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Shantha Kumara H, Jaspreet S, Pettke E, Miyagaki H, Herath SA, Yan X, Cekic V, Whelan RL. Osteopontin Levels Are Persistently Elevated for 4 weeks Following Minimally Invasive Colorectal Cancer Resection. Surg Innov 2023; 30:7-12. [PMID: 35225101 DOI: 10.1177/15533506211067889] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
INTRODUCTION Osteopontin (OPN) is an integrin binding phosphorylated glycoprotein secreted by macrophages and leukocytes that is found in extracellular fluids and sites of inflammation; various forms of CD44 serve as receptors. Osteopontin, expressed by numerous cancers, enhances tumor progression and angiogenesis via the PI3K/AKT and ERK mediated pathways in concert with Vascular Endothelial Growth Factor (VEGF); OPN also plays a role in wound healing. The impact of minimally invasive colorectal resection (MICR) for colorectal cancer (CRC) on plasma OPN levels is unknown. This study's goal was to assess blood levels during the first month after MICR. METHOD Patients undergoing MICR for CRC who were enrolled in an IRB approved tissue/prospective data bank for whom preoperative, postop Day (POD) 1, POD 3, and at least 1 late postop plasma sample (POD 7-34) were available were studied. Osteopontin levels were determined in duplicate via enzyme linked immunosorbent assay (ELISA) (results reported as mean ± SD). The Wilcoxon signed rank test was used for analysis (significance P < .05). RESULTS A total of 101 CRC patients (63% colon and 37% rectal) met study criteria. The mean preop OPN level was 89.2 ± 36.8 (ng/ml) for the entire group. Significantly elevated (P < .001) mean plasma levels were detected, vs preop, on POD1 (198.0 ± 67.4; n = 101), POD 3 (186.0 ± 72.6, n = 101), POD 7-13 (154.1 ± 70.2, n = 70), POD14-20 (146.7 ± 53.4, n=32), and POD 21-27 (123.0 ± 56.9, n = 25). No difference was noted at the POD 27-34 timepoint (P > .05). CONCLUSION Plasma OPN levels are significantly elevated over baseline for a month after MICR for CRC. The early rise in OPN levels may be related to the postop acute inflammatory response. The persistent elevation noted in weeks 2-4, however, may be a manifestation of wound healing in which OPN plays a role. Similar persistent plasma elevations of VEGF, angiopoietin 2 (ANG 2), and 11 other proangiogenic proteins have been noted and, collectively, may promote angiogenesis in residual tumors.
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Affiliation(s)
- Hmc Shantha Kumara
- Division of Colon and Rectal Surgery, Department of Surgery, 5945Lenox Hill Hospital, New York, NY, USA
| | - Sandhu Jaspreet
- Department of Surgery, 2025Brookdale University and Hospital Medical Center, Brooklyn, NY, USA
| | - Erica Pettke
- Department of colon and rectal surgery, 7287Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA
| | | | | | - Xiaohong Yan
- Division of Colon and Rectal Surgery, Department of Surgery, 5945Lenox Hill Hospital, New York, NY, USA
| | - Vesna Cekic
- Division of Colon and Rectal Surgery, Department of Surgery, 5945Lenox Hill Hospital, New York, NY, USA
| | - Richard L Whelan
- Division of Colon and Rectal Surgery, Department of Surgery, 5945Lenox Hill Hospital, New York, NY, USA.,Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
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Recent advances in the development of transplanted colorectal cancer mouse models. Transl Res 2022; 249:128-143. [PMID: 35850446 DOI: 10.1016/j.trsl.2022.07.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Revised: 06/13/2022] [Accepted: 07/11/2022] [Indexed: 11/22/2022]
Abstract
Despite progress in prevention and treatment, colorectal cancer (CRC) remains the third most common malignancy worldwide and the second most common cause of cancer death in 2020. To evaluate various characteristics of human CRC, a variety of mouse models have been established. Transplant mouse models have distinct advantages in studying the clinical behavior and therapeutic progress of CRC. Host, xenograft, and transplantation routes are the basis of transplant mouse models. As the effects of the tumor microenvironment and the systemic environment on cancer cells are gradually revealed, 3 key elements of transplanted CRC mouse models have been revolutionized. This has led to the development of humanized mice, patient-derived xenografts, and orthotopic transplants that reflect the human systemic environment, patient's tumor of origin, and tumor growth microenvironments in immunodeficient mice, respectively. These milestone events have allowed for great progress in tumor biology and the treatment of CRC. This article reviews the evolution of these events and points out their strengths and weaknesses as innovative and useful preclinical tools to study CRC progression and metastasis and to exploit novel treatment schedules by establishing a testing platform. This review article depicts the optimal transplanted CRC mouse models and emphasizes the significance of surgical models in the study of CRC behavior and treatment response.
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Colloca GA, Venturino A, Guarneri D. Primary tumor resection in patients with unresectable colorectal cancer with synchronous metastases could improve the activity of poly-chemotherapy: A trial-level meta-analysis. Surg Oncol 2022; 44:101820. [DOI: 10.1016/j.suronc.2022.101820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 06/12/2022] [Accepted: 07/11/2022] [Indexed: 12/24/2022]
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Shinozaki H, Matsuoka T, Ozawa S. Pharmacological treatment to reduce pulmonary morbidity after esophagectomy. Ann Gastroenterol Surg 2021; 5:614-622. [PMID: 34585046 PMCID: PMC8452480 DOI: 10.1002/ags3.12469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 03/29/2021] [Accepted: 04/14/2021] [Indexed: 11/10/2022] Open
Abstract
Esophagectomy for esophageal cancer is one of the most invasive procedures in gastrointestinal surgery. An invasive surgical procedure causes postoperative lung injury through the surgical procedure and one-lung ventilation during anesthesia. Lung injury developed by inflammatory response to surgical insults and oxidative stress is associated with pulmonary morbidity after esophagectomy. Postoperative pulmonary complications negatively affect the long-term outcomes; therefore, an effort to reduce lung injury improves overall survival after esophagectomy. Although significant evidence has not been established, various pharmacological treatments for reducing lung injury, such as administration of a corticosteroid, neutrophil elastase inhibitor, and vitamins are considered to have efficacy for pulmonary morbidity. In this review we survey the following topics: mediators during the perioperative periods of esophagectomy and the efficacy of pharmacological therapies for patients with esophagectomy on pulmonary complications.
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Affiliation(s)
| | | | - Soji Ozawa
- Department of Gastroenterological SurgeryTokai University School of MedicineKanagawaJapan
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Immunophenotype Rearrangement in Response to Tumor Excision May Be Related to the Risk of Biochemical Recurrence in Prostate Cancer Patients. J Clin Med 2021; 10:jcm10163709. [PMID: 34442004 PMCID: PMC8396861 DOI: 10.3390/jcm10163709] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Revised: 08/10/2021] [Accepted: 08/16/2021] [Indexed: 02/07/2023] Open
Abstract
Background: Prostate cancer (PCa) is known to exhibit a wide spectrum of aggressiveness and relatively high immunogenicity. The aim of this study was to examine the effect of tumor excision on immunophenotype rearrangements in peripheral blood and to elucidate if it is associated with biochemical recurrence (BCR) in high risk (HR) and low risk (LR) patients. Methods: Radical prostatectomy (RP) was performed on 108 PCa stage pT2–pT3 patients. Preoperative vs. postoperative (one and three months) immunophenotype profile (T- and B-cell subsets, MDSC, NK, and T reg populations) was compared in peripheral blood of LR and HR groups. Results: The BCR-free survival difference was significant between the HR and LR groups. Postoperative PSA decay rate, defined as ePSA, was significantly slower in the HR group and predicted BCR at cut-off level ePSA = −2.0% d−1 (AUC = 0.85 (95% CI, 0.78–0.90). Three months following tumor excision, the LR group exhibited a recovery of natural killer CD3 − CD16+ CD56+ cells, from 232 cells/µL to 317 cells/µL (p < 0.05), which was not detectable in the HR group. Prostatectomy also resulted in an increased CD8+ population in the LR group, mostly due to CD8+ CD69+ compartment (from 186 cells/µL before surgery to 196 cells/µL three months after, p < 001). The CD8+ CD69+ subset increase without total T cell increase was present in the HR group (p < 0.001). Tumor excision resulted in a myeloid-derived suppressor cell (MDSC) number increase from 12.4 cells/µL to 16.2 cells/µL in the HR group, and no change was detectable in LR patients (p = 0.12). An immune signature of postoperative recovery was more likely to occur in patients undergoing laparoscopic radical prostatectomy (LRP). Open RP (ORP) was associated with increased MDSC numbers (p = 0.002), whereas LRP was characterized by an immunity sparing profile, with no change in MDSC subset (p = 0.16). Conclusion: Tumor excision in prostate cancer patients results in two distinct patterns of immunophenotype rearrangement. The low-risk group is highly responsive, revealing postoperative restoration of T cells, NK cells, and CD8+ CD69+ numbers and the absence of suppressor MDSC increase. The high-risk group presented a limited response, accompanied by a suppressor MDSC increase and CD8+ CD69+ increase. The laparoscopic approach, unlike ORP, did not result in an MDSC increase in the postoperative period.
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Shantha Kumara HMC, Miyagaki H, Herath SA, Pettke E, Yan X, Cekic V, Whelan RL. Plasma MMP-2 and MMP-7 levels are elevated first month after surgery and may promote growth of residual metastases. World J Gastrointest Oncol 2021; 13:879-892. [PMID: 34457193 PMCID: PMC8371512 DOI: 10.4251/wjgo.v13.i8.879] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 03/16/2021] [Accepted: 06/04/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND MMP-2 also known as gelatinase A and MMP-7 (matrilysin) are members of the zinc-dependent family of MMPs (Matrix metalloproteinase). MMP-2 and MMP-7 are remodeling enzymes that digest extracellular matrix; MMP-2 is extensively expressed during development and is upregulated at sites of tissue damage, inflammation, and in stromal cells of metastatic tumors. MMP-7 is expressed in the epithelial cells and in a variety of cancers including colon tumors. Plasma MMP-2 and MMP-7 levels were assessed before and after minimally invasive colorectal resection for cancer pathology.
AIM To determine plasma MMP-2 and MMP-7 levels before and after minimally invasive colorectal resection for cancer pathology.
METHODS Patients enrolled in a plasma bank for whom plasma was available were eligible. Plasma obtained from preoperative (Preop) and postoperative blood samples was used. Only colorectal cancer (CRC) patients who underwent elective minimally invasive cancer resection with preop, post-operative day (POD) 1, 3 and at least 1 late postop sample (POD 7-34) were included. Late samples were bundled into 7 d blocks (POD 7-13, 14-20, etc.) and treated as single time points. Plasma MMP-2 and MMP-7 levels were determined via enzyme-linked immunosorbent assay in duplicate.
RESULTS Total 88 minimally invasive CRC resection CRC patients were studied (right colectomy, 37%; sigmoid, 24%; and LAR/AR 18%). Cancer stages were: 1, 31%; 2, 30%; 3, 34%; and 4, 5%. Mean Preop MMP-2 plasma level (ng/mL) was 179.3 ± 40.9 (n = 88). Elevated mean levels were noted on POD1 (214.3 ± 51.2, n = 87, P < 0.001), POD3 (258.0 ± 63.9, n = 80, P < 0.001), POD7-13 (229.9 ± 62.3, n = 65, P < 0.001), POD 14-20 (234.9 ± 47.5, n = 25, P < 0.001), POD 21-27 (237.0 ± 63.5, n = 17, P < 0.001,) and POD 28-34 (255.4 ± 59.7, n = 15, P < 0.001). Mean Preop MMP-7 level was 3.9 ± 1.9 (n = 88). No significant differences were noted on POD 1 or 3, however, significantly elevated levels were noted on POD 7-13 (5.7 ± 2.5, n = 65, P < 0.001), POD 14-20 (5.9 ± 2.5, n = 25, P < 0.001), POD 21-27 (6.1 ± 3.6, n = 17, P = 0.002) and on POD 28-34 (6.8 ± 3.3, n = 15 P < 0.001,) vs preop levels.
CONCLUSION MMP-2 levels are elevated for 5 wk and MMP-7 levels elevated for weeks 2-6. The etiology of these changes in unclear, trauma and wound healing likely play a role. These changes may promote residual tumor growth and metastasis.
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Affiliation(s)
- HMC Shantha Kumara
- Division of Colon and Rectal Surgery, Department of Surgery, Lenox Hill Hospital, Northwell Health, New York, NY 10028, United States
| | - Hiromichi Miyagaki
- Department of Gastroenterological Surgery, Osaka University, Suita 565-0862, Osaka, Japan
| | - Sajith A Herath
- Analytic Department, Novartis, Morris Plains, NJ 07905, United States
| | - Erica Pettke
- Department of Surgery, Swedish Medical Center, Seattle, WA 98122, United States
| | - Xiaohong Yan
- Division of Colon and Rectal Surgery, Department of Surgery, Lenox Hill Hospital, Northwell Health, New York, NY 10028, United States
| | - Vesna Cekic
- Division of Colon and Rectal Surgery, Department of Surgery, Lenox Hill Hospital, Northwell Health, New York, NY 10028, United States
| | - Richard L Whelan
- Division of Colon and Rectal Surgery, Department of Surgery, Lenox Hill Hospital, Northwell Health, New York, NY 10028, United States
- Department of Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, United States
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Verma A, Kumar S. Laparoscopy in Colonic Cancer. Indian J Surg 2021. [DOI: 10.1007/s12262-019-02054-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
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Shantha Kumara HMC, Pettke E, Shah A, Yan X, Cekic V, Downing MA, Gandhi ND, Whelan RL. Plasma levels of the proangiogenic protein CXCL16 remains elevated for 1 month after minimally invasive colorectal cancer resection. World J Surg Oncol 2018; 16:132. [PMID: 29981574 PMCID: PMC6035800 DOI: 10.1186/s12957-018-1418-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Accepted: 06/20/2018] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Inflammation-induced endothelial precursor cell recruitment and angiogenesis are thought to be associated with CXCL16-CXCR6 pair activity. This study's main purpose was to determine plasma CXCL16 levels after minimally invasive colorectal resection (MICR) for colorectal cancer (CRC); an adjunct study assessed wound fluid (WF) and plasma CXCL16 levels in a separate group of CRC patients. METHODS CRC patients who had MICR and for whom plasma was available in a tissue bank were eligible. Plasma samples were collected preoperatively from all patients. Samples were also collected on postoperative days (POD) 1 and 3 and at various late postoperative time points (POD 7-34). In a separate study, blood and intra-abdominal wound fluid (WF) samples were collected from CRC MICR patients (pts). Samples were stored at - 80 °C. CXCL16 levels were determined via ELISA. The Wilcoxon signed-rank and Mann and Whitney tests were used for analysis. RESULTS Main study: 86 CRC pts. were included. The mean preoperative plasma CXCL16 level was 2.36 ± 0.57 ng/ml. Elevated mean plasma levels (p < 0.0001 × first 4 time points) were noted on POD 1 (2.82 ± 0.81, n = 86), POD 3 (3.12 ± 0.77, n = 82), POD 7-13 (3.28 ± 0.88, n = 64), POD 14-20 (3.03 ± 0.62, n = 24), POD 21-27 (3.06 ± 0.67, n = 20, p = 0.0003), and POD 28-34 (3.17 ± 0.43, n = 11, p = 0.001) vs. preop levels. WF study: In the adjunct study, plasma and WF CXCL16 levels were determined for 23 CRC MICR pts. WF levels at all time points were significantly elevated over plasma levels. CONCLUSION Plasma CXCL16 levels were elevated for 4 weeks after minimally invasive colorectal resection for cancer. Also, WF CXCL16 levels were 3-10 times greater than the corresponding plasma concentrations. The source of the late plasma elevations may be the healing wound. Increased plasma CXCL16 levels may promote tumor angiogenesis in the first month after MICR.
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Affiliation(s)
- H. M. C. Shantha Kumara
- Division of Colon and Rectal Surgery, Department of Surgery, Mount Sinai West Hospital, Suite 7B, 425 West, 59th Street, New York, NY 10019 USA
| | - Erica Pettke
- Division of Colon and Rectal Surgery, Department of Surgery, Mount Sinai West Hospital, Suite 7B, 425 West, 59th Street, New York, NY 10019 USA
| | - Abhinit Shah
- Division of Colon and Rectal Surgery, Department of Surgery, Mount Sinai West Hospital, Suite 7B, 425 West, 59th Street, New York, NY 10019 USA
| | - Xiaohong Yan
- Division of Colon and Rectal Surgery, Department of Surgery, Mount Sinai West Hospital, Suite 7B, 425 West, 59th Street, New York, NY 10019 USA
| | - Vesna Cekic
- Division of Colon and Rectal Surgery, Department of Surgery, Mount Sinai West Hospital, Suite 7B, 425 West, 59th Street, New York, NY 10019 USA
| | - Melissa Alvarez Downing
- Division of Colon and Rectal Surgery, Department of Surgery, Mount Sinai West Hospital, Suite 7B, 425 West, 59th Street, New York, NY 10019 USA
| | - Nipa Dilip Gandhi
- Division of Colon and Rectal Surgery, Department of Surgery, Mount Sinai West Hospital, Suite 7B, 425 West, 59th Street, New York, NY 10019 USA
| | - Richard L. Whelan
- Division of Colon and Rectal Surgery, Department of Surgery, Mount Sinai West Hospital, Suite 7B, 425 West, 59th Street, New York, NY 10019 USA
- Icahn School of Medicine at Mount Sinai, New York, NY 10029 USA
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Ziogas IA, Tsoulfas G. Advances and challenges in laparoscopic surgery in the management of hepatocellular carcinoma. World J Gastrointest Surg 2017; 9:233-245. [PMID: 29359029 PMCID: PMC5752958 DOI: 10.4240/wjgs.v9.i12.233] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Revised: 11/04/2017] [Accepted: 12/05/2017] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma is the fifth most common malignancy and the third most common cause of cancer-related mortality worldwide. From the wide variety of treatment options, surgical resection and liver transplantation are the only therapeutic ones. However, due to shortage of liver grafts, surgical resection is the most common therapeutic modality implemented. Owing to rapid technological development, minimally invasive approaches have been incorporated in liver surgery. Liver laparoscopic resection has been evaluated in comparison to the open technique and has been shown to be superior because of the reported decrease in surgical incision length and trauma, blood loss, operating theatre time, postsurgical pain and complications, R0 resection, length of stay, time to recovery and oral intake. It has been reported that laparoscopic excision is a safe and feasible approach with near zero mortality and oncologic outcomes similar to open resection. Nevertheless, current indications include solid tumors in the periphery < 5 cm, especially in segments II through VI, while according to the consensus laparoscopic major hepatectomy should only be performed by surgeons with high expertise in laparoscopic and hepatobiliary surgery in tertiary centers. It is necessary for a surgeon to surpass the 60-cases learning curve observed in order to accomplish the desirable outcomes and preserve patient safety. In this review, our aim is to thoroughly describe the general principles and current status of laparoscopic liver resection for hepatocellular carcinoma, as well as future prospects.
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Affiliation(s)
- Ioannis A Ziogas
- Medical School, Aristotle University of Thessaloniki, Thessaloniki 54453, Greece
| | - Georgios Tsoulfas
- Associate Professor of Surgery, 1st Department of Surgery, Aristotle University of Thessaloniki, Thessaloniki 54453, Greece
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Ba MC, Long H, Zhang XL, Gong YF, Yan ZF, Wang S, Tang YQ, Cui SZ. Port-Site Metastases and Chimney Effect of B-Ultrasound-Guided and Laparoscopically-Assisted Hyperthermic Intraperitoneal Perfusion Chemotherapy. Yonsei Med J 2017; 58:497-504. [PMID: 28332353 PMCID: PMC5368133 DOI: 10.3349/ymj.2017.58.3.497] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Revised: 10/10/2015] [Accepted: 10/26/2015] [Indexed: 12/15/2022] Open
Abstract
PURPOSE CO₂ leakage along the trocar (chimney effect) has been proposed to be an important factor underlying port-site metastasis after laparoscopic surgery. This study aimed to test this hypothesis by comparing the incidence of port-site metastasis between B-ultrasound-guided and laparoscopically-assisted hyperthermic intraperitoneal perfusion chemotherapy (HIPPC). MATERIALS AND METHODS Sixty-two patients with malignant ascites induced by gastrointestinal or ovarian cancer were divided into two groups to receive either B-ultrasound-guided or laparoscopically-assisted HIPPC. Clinical efficacy was assessed from the objective remission rate (ORR), the Karnofsky Performance Status (KPS) score, and overall survival. The incidence of port-site metastasis was compared between the two groups. RESULTS Patients in the B-ultrasound (n=32) and laparoscopy (n=30) groups were comparable in terms of age, sex, primary disease type, volume of ascites, and free cancer cell (FCC)-positive ascites. After HIPPC, there were no significant differences between the B-ultrasound and laparoscopy groups in the KPS score change, ORR, and median survival time. The incidence of port-site metastasis after HIPPC was not significantly different between the B-ultrasound (3 of 32, 9.36%) and laparoscopy (3 of 30, 10%) groups, but significantly different among pancreatic, gastric, ovarian, and colorectal cancer (33.33, 15.79, 10.00, and 0.00%, p<0.001). CONCLUSION The chimney effect may not be the key reason for port-site metastasis after laparoscopy. Other factors may play a role, including the local microenvironment at the trocar site and the delivery of viable FCCs (from the tumor or malignant ascites) to the trauma site during laparoscopic surgery.
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Affiliation(s)
- Ming Chen Ba
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Center of Guangzhou Medical University, Guangzhou, P.R. China.
| | - Hui Long
- Department of Pharmacy, Guangzhou Dermatology Institute, Guangzhou, P.R. China.
| | - Xiang Liang Zhang
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Center of Guangzhou Medical University, Guangzhou, P.R. China
| | - Yuan Feng Gong
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Center of Guangzhou Medical University, Guangzhou, P.R. China
| | - Zhao Fei Yan
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Center of Guangzhou Medical University, Guangzhou, P.R. China
| | - Shuai Wang
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Center of Guangzhou Medical University, Guangzhou, P.R. China
| | - Yun Qiang Tang
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Center of Guangzhou Medical University, Guangzhou, P.R. China
| | - Shu Zhong Cui
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Center of Guangzhou Medical University, Guangzhou, P.R. China
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Bryan RB, Gough MJ, Seung SK, Jutric Z, Weinberg AD, Fox BA, Crittenden MR, Leidner RS, Curti B. Cytoreductive surgery for head and neck squamous cell carcinoma in the new age of immunotherapy. Oral Oncol 2016; 61:166-76. [PMID: 27614589 DOI: 10.1016/j.oraloncology.2016.08.020] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Accepted: 08/30/2016] [Indexed: 12/11/2022]
Abstract
Cytoreductive surgery is an approach to cancer treatment that aims to reduce the number of cancer cells via resection of primary tumor or metastatic deposits, in an effort to minimize a potentially immunosuppressive tumor burden, palliate symptoms, and prevent complications. Furthermore, it provides a platform for investigation of biomarkers with the goal of optimizing immunotherapy to reverse the immunosuppressive tumor microenvironment and enhance adaptive immune responses. Ultimately, our group aims to exploit the concept that successful cancer therapy is dependent upon an effective immune response. Surgery will remain an integral part of head and neck squamous cell carcinoma (HNSCC) treatment in the future, even as checkpoint inhibitors, co-stimulatory molecules, vaccines, adoptive T cell therapy and other novel agents enter clinical routine. Cytoreductive resection may provide an effective platform for immunotherapy and biomarker directed interventions to improve outcomes for patients with HNSCC.
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Affiliation(s)
- R Bryan Bryan
- Earle A. Chiles Research Institute at Providence Cancer Center, 4805 NE Glisan St. Suite 2N35, Portland, OR 97213, United States; Providence Oral, Head and Neck Cancer Program and Clinic, Providence Cancer Center, Providence Portland Medical Center, 4805 NE Glisan St. Suite 6N50, Portland, OR 97213, United States; Head and Neck Institute, 1849 NW Kearney, Suite 300, Portland, OR 97209, United States.
| | - Michael J Gough
- Earle A. Chiles Research Institute at Providence Cancer Center, 4805 NE Glisan St. Suite 2N35, Portland, OR 97213, United States
| | - Steven K Seung
- Earle A. Chiles Research Institute at Providence Cancer Center, 4805 NE Glisan St. Suite 2N35, Portland, OR 97213, United States; Providence Oral, Head and Neck Cancer Program and Clinic, Providence Cancer Center, Providence Portland Medical Center, 4805 NE Glisan St. Suite 6N50, Portland, OR 97213, United States; The Oregon Clinic, Department of Radiation Oncology, 4805 NE Glisan St., Portland, OR 97213, United States
| | - Zeljka Jutric
- Earle A. Chiles Research Institute at Providence Cancer Center, 4805 NE Glisan St. Suite 2N35, Portland, OR 97213, United States
| | - Andrew D Weinberg
- Earle A. Chiles Research Institute at Providence Cancer Center, 4805 NE Glisan St. Suite 2N35, Portland, OR 97213, United States
| | - Bernard A Fox
- Earle A. Chiles Research Institute at Providence Cancer Center, 4805 NE Glisan St. Suite 2N35, Portland, OR 97213, United States
| | - Marka R Crittenden
- Earle A. Chiles Research Institute at Providence Cancer Center, 4805 NE Glisan St. Suite 2N35, Portland, OR 97213, United States; Providence Oral, Head and Neck Cancer Program and Clinic, Providence Cancer Center, Providence Portland Medical Center, 4805 NE Glisan St. Suite 6N50, Portland, OR 97213, United States; The Oregon Clinic, Department of Radiation Oncology, 4805 NE Glisan St., Portland, OR 97213, United States
| | - Rom S Leidner
- Earle A. Chiles Research Institute at Providence Cancer Center, 4805 NE Glisan St. Suite 2N35, Portland, OR 97213, United States; Providence Oral, Head and Neck Cancer Program and Clinic, Providence Cancer Center, Providence Portland Medical Center, 4805 NE Glisan St. Suite 6N50, Portland, OR 97213, United States
| | - Brendan Curti
- Earle A. Chiles Research Institute at Providence Cancer Center, 4805 NE Glisan St. Suite 2N35, Portland, OR 97213, United States
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Block KI, Gyllenhaal C, Lowe L, Amedei A, Amin ARMR, Amin A, Aquilano K, Arbiser J, Arreola A, Arzumanyan A, Ashraf SS, Azmi AS, Benencia F, Bhakta D, Bilsland A, Bishayee A, Blain SW, Block PB, Boosani CS, Carey TE, Carnero A, Carotenuto M, Casey SC, Chakrabarti M, Chaturvedi R, Chen GZ, Chen H, Chen S, Chen YC, Choi BK, Ciriolo MR, Coley HM, Collins AR, Connell M, Crawford S, Curran CS, Dabrosin C, Damia G, Dasgupta S, DeBerardinis RJ, Decker WK, Dhawan P, Diehl AME, Dong JT, Dou QP, Drew JE, Elkord E, El-Rayes B, Feitelson MA, Felsher DW, Ferguson LR, Fimognari C, Firestone GL, Frezza C, Fujii H, Fuster MM, Generali D, Georgakilas AG, Gieseler F, Gilbertson M, Green MF, Grue B, Guha G, Halicka D, Helferich WG, Heneberg P, Hentosh P, Hirschey MD, Hofseth LJ, Holcombe RF, Honoki K, Hsu HY, Huang GS, Jensen LD, Jiang WG, Jones LW, Karpowicz PA, Keith WN, Kerkar SP, Khan GN, Khatami M, Ko YH, Kucuk O, Kulathinal RJ, Kumar NB, Kwon BS, Le A, Lea MA, Lee HY, Lichtor T, Lin LT, Locasale JW, Lokeshwar BL, Longo VD, Lyssiotis CA, MacKenzie KL, Malhotra M, Marino M, Martinez-Chantar ML, Matheu A, Maxwell C, McDonnell E, Meeker AK, Mehrmohamadi M, Mehta K, Michelotti GA, Mohammad RM, Mohammed SI, Morre DJ, Muralidhar V, Muqbil I, Murphy MP, Nagaraju GP, Nahta R, Niccolai E, Nowsheen S, Panis C, Pantano F, Parslow VR, Pawelec G, Pedersen PL, Poore B, Poudyal D, Prakash S, Prince M, Raffaghello L, Rathmell JC, Rathmell WK, Ray SK, Reichrath J, Rezazadeh S, Ribatti D, Ricciardiello L, Robey RB, Rodier F, Rupasinghe HPV, Russo GL, Ryan EP, Samadi AK, Sanchez-Garcia I, Sanders AJ, Santini D, Sarkar M, Sasada T, Saxena NK, Shackelford RE, Shantha Kumara HMC, Sharma D, Shin DM, Sidransky D, Siegelin MD, Signori E, Singh N, Sivanand S, Sliva D, Smythe C, Spagnuolo C, Stafforini DM, Stagg J, Subbarayan PR, Sundin T, Talib WH, Thompson SK, Tran PT, Ungefroren H, Vander Heiden MG, Venkateswaran V, Vinay DS, Vlachostergios PJ, Wang Z, Wellen KE, Whelan RL, Yang ES, Yang H, Yang X, Yaswen P, Yedjou C, Yin X, Zhu J, Zollo M. Designing a broad-spectrum integrative approach for cancer prevention and treatment. Semin Cancer Biol 2016; 35 Suppl:S276-S304. [PMID: 26590477 DOI: 10.1016/j.semcancer.2015.09.007] [Citation(s) in RCA: 190] [Impact Index Per Article: 21.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Revised: 08/12/2015] [Accepted: 09/14/2015] [Indexed: 12/14/2022]
Abstract
Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered.
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Affiliation(s)
- Keith I Block
- Block Center for Integrative Cancer Treatment, Skokie, IL, United States.
| | | | - Leroy Lowe
- Getting to Know Cancer, Truro, Nova Scotia, Canada; Lancaster Environment Centre, Lancaster University, Bailrigg, Lancaster, United Kingdom.
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - A R M Ruhul Amin
- Winship Cancer Institute of Emory University, Atlanta, GA, United States
| | - Amr Amin
- Department of Biology, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Katia Aquilano
- Department of Biology, University of Rome "Tor Vergata", Rome, Italy
| | - Jack Arbiser
- Winship Cancer Institute of Emory University, Atlanta, GA, United States; Atlanta Veterans Administration Medical Center, Atlanta, GA, United States; Department of Dermatology, Emory University School of Medicine, Emory University, Atlanta, GA, United States
| | - Alexandra Arreola
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States
| | - Alla Arzumanyan
- Department of Biology, Temple University, Philadelphia, PA, United States
| | - S Salman Ashraf
- Department of Chemistry, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Asfar S Azmi
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States
| | - Fabian Benencia
- Department of Biomedical Sciences, Ohio University, Athens, OH, United States
| | - Dipita Bhakta
- School of Chemical and Bio Technology, SASTRA University, Thanjavur, Tamil Nadu, India
| | | | - Anupam Bishayee
- Department of Pharmaceutical Sciences, College of Pharmacy, Larkin Health Sciences Institute, Miami, FL, United States
| | - Stacy W Blain
- Department of Pediatrics, State University of New York, Downstate Medical Center, Brooklyn, NY, United States
| | - Penny B Block
- Block Center for Integrative Cancer Treatment, Skokie, IL, United States
| | - Chandra S Boosani
- Department of BioMedical Sciences, School of Medicine, Creighton University, Omaha, NE, United States
| | - Thomas E Carey
- Head and Neck Cancer Biology Laboratory, University of Michigan, Ann Arbor, MI, United States
| | - Amancio Carnero
- Instituto de Biomedicina de Sevilla, Consejo Superior de Investigaciones Cientificas, Seville, Spain
| | - Marianeve Carotenuto
- Centro di Ingegneria Genetica e Biotecnologia Avanzate, Naples, Italy; Department of Molecular Medicine and Medical Biotechnology, Federico II, Via Pansini 5, 80131 Naples, Italy
| | - Stephanie C Casey
- Stanford University, Division of Oncology, Department of Medicine and Pathology, Stanford, CA, United States
| | - Mrinmay Chakrabarti
- Department of Pathology, Microbiology, and Immunology, University of South Carolina, School of Medicine, Columbia, SC, United States
| | - Rupesh Chaturvedi
- School of Biotechnology, Jawaharlal Nehru University, New Delhi, India
| | - Georgia Zhuo Chen
- Winship Cancer Institute of Emory University, Atlanta, GA, United States
| | - Helen Chen
- Department of Pediatrics, University of British Columbia, Michael Cuccione Childhood Cancer Research Program, Child and Family Research Institute, Vancouver, British Columbia, Canada
| | - Sophie Chen
- Ovarian and Prostate Cancer Research Laboratory, Guildford, Surrey, United Kingdom
| | - Yi Charlie Chen
- Department of Biology, Alderson Broaddus University, Philippi, WV, United States
| | - Beom K Choi
- Cancer Immunology Branch, Division of Cancer Biology, National Cancer Center, Goyang, Gyeonggi, Republic of Korea
| | | | - Helen M Coley
- Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United Kingdom
| | - Andrew R Collins
- Department of Nutrition, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Marisa Connell
- Department of Pediatrics, University of British Columbia, Michael Cuccione Childhood Cancer Research Program, Child and Family Research Institute, Vancouver, British Columbia, Canada
| | - Sarah Crawford
- Cancer Biology Research Laboratory, Southern Connecticut State University, New Haven, CT, United States
| | - Colleen S Curran
- School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Charlotta Dabrosin
- Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
| | - Giovanna Damia
- Department of Oncology, Istituto Di Ricovero e Cura a Carattere Scientifico - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
| | - Santanu Dasgupta
- Department of Cellular and Molecular Biology, the University of Texas Health Science Center at Tyler, Tyler, TX, United States
| | - Ralph J DeBerardinis
- Children's Medical Center Research Institute, University of Texas - Southwestern Medical Center, Dallas, TX, United States
| | - William K Decker
- Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, United States
| | - Punita Dhawan
- Department of Surgery and Cancer Biology, Division of Surgical Oncology, Vanderbilt University School of Medicine, Nashville, TN, United States
| | - Anna Mae E Diehl
- Department of Medicine, Duke University Medical Center, Durham, NC, United States
| | - Jin-Tang Dong
- Winship Cancer Institute of Emory University, Atlanta, GA, United States
| | - Q Ping Dou
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States
| | - Janice E Drew
- Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, Scotland, United Kingdom
| | - Eyad Elkord
- College of Medicine & Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Bassel El-Rayes
- Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, United States
| | - Mark A Feitelson
- Department of Biology, Temple University, Philadelphia, PA, United States
| | - Dean W Felsher
- Stanford University, Division of Oncology, Department of Medicine and Pathology, Stanford, CA, United States
| | - Lynnette R Ferguson
- Discipline of Nutrition and Auckland Cancer Society Research Centre, University of Auckland, Auckland, New Zealand
| | - Carmela Fimognari
- Dipartimento di Scienze per la Qualità della Vita Alma Mater Studiorum-Università di Bologna, Rimini, Italy
| | - Gary L Firestone
- Department of Molecular & Cell Biology, University of California Berkeley, Berkeley, CA, United States
| | - Christian Frezza
- Medical Research Council Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge, United Kingdom
| | - Hiromasa Fujii
- Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan
| | - Mark M Fuster
- Medicine and Research Services, Veterans Affairs San Diego Healthcare System & University of California, San Diego, CA, United States
| | - Daniele Generali
- Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy; Molecular Therapy and Pharmacogenomics Unit, Azienda Ospedaliera Istituti Ospitalieri di Cremona, Cremona, Italy
| | - Alexandros G Georgakilas
- Physics Department, School of Applied Mathematics and Physical Sciences, National Technical University of Athens, Athens, Greece
| | - Frank Gieseler
- First Department of Medicine, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | | | - Michelle F Green
- Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, United States
| | - Brendan Grue
- Departments of Environmental Science, Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Gunjan Guha
- School of Chemical and Bio Technology, SASTRA University, Thanjavur, Tamil Nadu, India
| | - Dorota Halicka
- Department of Pathology, New York Medical College, Valhalla, NY, United States
| | | | - Petr Heneberg
- Charles University in Prague, Third Faculty of Medicine, Prague, Czech Republic
| | - Patricia Hentosh
- School of Medical Laboratory and Radiation Sciences, Old Dominion University, Norfolk, VA, United States
| | - Matthew D Hirschey
- Department of Medicine, Duke University Medical Center, Durham, NC, United States; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, United States
| | - Lorne J Hofseth
- College of Pharmacy, University of South Carolina, Columbia, SC, United States
| | - Randall F Holcombe
- Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY, United States
| | - Kanya Honoki
- Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan
| | - Hsue-Yin Hsu
- Department of Life Sciences, Tzu-Chi University, Hualien, Taiwan
| | - Gloria S Huang
- Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, United States
| | - Lasse D Jensen
- Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
| | - Wen G Jiang
- Cardiff University School of Medicine, Heath Park, Cardiff, United Kingdom
| | - Lee W Jones
- Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, United States
| | | | | | - Sid P Kerkar
- Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States
| | | | - Mahin Khatami
- Inflammation and Cancer Research, National Cancer Institute (Retired), National Institutes of Health, Bethesda, MD, United States
| | - Young H Ko
- University of Maryland BioPark, Innovation Center, KoDiscovery, Baltimore, MD, United States
| | - Omer Kucuk
- Winship Cancer Institute of Emory University, Atlanta, GA, United States
| | - Rob J Kulathinal
- Department of Biology, Temple University, Philadelphia, PA, United States
| | - Nagi B Kumar
- Moffitt Cancer Center, University of South Florida College of Medicine, Tampa, FL, United States
| | - Byoung S Kwon
- Cancer Immunology Branch, Division of Cancer Biology, National Cancer Center, Goyang, Gyeonggi, Republic of Korea; Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA, United States
| | - Anne Le
- The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Michael A Lea
- New Jersey Medical School, Rutgers University, Newark, NJ, United States
| | - Ho-Young Lee
- College of Pharmacy, Seoul National University, South Korea
| | - Terry Lichtor
- Department of Neurosurgery, Rush University Medical Center, Chicago, IL, United States
| | - Liang-Tzung Lin
- Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Jason W Locasale
- Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States
| | - Bal L Lokeshwar
- Department of Medicine, Georgia Regents University Cancer Center, Augusta, GA, United States
| | - Valter D Longo
- Andrus Gerontology Center, Division of Biogerontology, University of Southern California, Los Angeles, CA, United States
| | - Costas A Lyssiotis
- Department of Molecular and Integrative Physiology and Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, United States
| | - Karen L MacKenzie
- Children's Cancer Institute Australia, Kensington, New South Wales, Australia
| | - Meenakshi Malhotra
- Department of Biomedical Engineering, McGill University, Montréal, Canada
| | - Maria Marino
- Department of Science, University Roma Tre, Rome, Italy
| | - Maria L Martinez-Chantar
- Metabolomic Unit, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Technology Park of Bizkaia, Bizkaia, Spain
| | | | - Christopher Maxwell
- Department of Pediatrics, University of British Columbia, Michael Cuccione Childhood Cancer Research Program, Child and Family Research Institute, Vancouver, British Columbia, Canada
| | - Eoin McDonnell
- Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, United States
| | - Alan K Meeker
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Mahya Mehrmohamadi
- Field of Genetics, Genomics, and Development, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, United States
| | - Kapil Mehta
- Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Gregory A Michelotti
- Department of Medicine, Duke University Medical Center, Durham, NC, United States
| | - Ramzi M Mohammad
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States
| | - Sulma I Mohammed
- Department of Comparative Pathobiology, Purdue University Center for Cancer Research, West Lafayette, IN, United States
| | - D James Morre
- Mor-NuCo, Inc, Purdue Research Park, West Lafayette, IN, United States
| | - Vinayak Muralidhar
- Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA, United States; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States
| | - Irfana Muqbil
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States
| | - Michael P Murphy
- MRC Mitochondrial Biology Unit, Wellcome Trust-MRC Building, Hills Road, Cambridge, United Kingdom
| | | | - Rita Nahta
- Winship Cancer Institute of Emory University, Atlanta, GA, United States
| | | | - Somaira Nowsheen
- Medical Scientist Training Program, Mayo Graduate School, Mayo Medical School, Mayo Clinic, Rochester, MN, United States
| | - Carolina Panis
- Laboratory of Inflammatory Mediators, State University of West Paraná, UNIOESTE, Paraná, Brazil
| | - Francesco Pantano
- Medical Oncology Department, University Campus Bio-Medico, Rome, Italy
| | - Virginia R Parslow
- Discipline of Nutrition and Auckland Cancer Society Research Centre, University of Auckland, Auckland, New Zealand
| | - Graham Pawelec
- Center for Medical Research, University of Tübingen, Tübingen, Germany
| | - Peter L Pedersen
- Departments of Biological Chemistry and Oncology, Member at Large, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, School of Medicine, Baltimore, MD, United States
| | - Brad Poore
- The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Deepak Poudyal
- College of Pharmacy, University of South Carolina, Columbia, SC, United States
| | - Satya Prakash
- Department of Biomedical Engineering, McGill University, Montréal, Canada
| | - Mark Prince
- Department of Otolaryngology-Head and Neck, Medical School, University of Michigan, Ann Arbor, MI, United States
| | | | - Jeffrey C Rathmell
- Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, United States
| | - W Kimryn Rathmell
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States
| | - Swapan K Ray
- Department of Pathology, Microbiology, and Immunology, University of South Carolina, School of Medicine, Columbia, SC, United States
| | - Jörg Reichrath
- Center for Clinical and Experimental Photodermatology, Clinic for Dermatology, Venerology and Allergology, The Saarland University Hospital, Homburg, Germany
| | - Sarallah Rezazadeh
- Department of Biology, University of Rochester, Rochester, NY, United States
| | - Domenico Ribatti
- Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy & National Cancer Institute Giovanni Paolo II, Bari, Italy
| | - Luigi Ricciardiello
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - R Brooks Robey
- White River Junction Veterans Affairs Medical Center, White River Junction, VT, United States; Geisel School of Medicine at Dartmouth, Hanover, NH, United States
| | - Francis Rodier
- Centre de Rechercher du Centre Hospitalier de l'Université de Montréal and Institut du Cancer de Montréal, Montréal, Quebec, Canada; Université de Montréal, Département de Radiologie, Radio-Oncologie et Médicine Nucléaire, Montréal, Quebec, Canada
| | - H P Vasantha Rupasinghe
- Department of Environmental Sciences, Faculty of Agriculture and Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Gian Luigi Russo
- Institute of Food Sciences National Research Council, Avellino, Italy
| | - Elizabeth P Ryan
- Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, United States
| | | | - Isidro Sanchez-Garcia
- Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-Universidad de Salamanca, Salamanca, Spain
| | - Andrew J Sanders
- Cardiff University School of Medicine, Heath Park, Cardiff, United Kingdom
| | - Daniele Santini
- Medical Oncology Department, University Campus Bio-Medico, Rome, Italy
| | - Malancha Sarkar
- Department of Biology, University of Miami, Miami, FL, United States
| | - Tetsuro Sasada
- Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
| | - Neeraj K Saxena
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Rodney E Shackelford
- Department of Pathology, Louisiana State University, Health Shreveport, Shreveport, LA, United States
| | - H M C Shantha Kumara
- Department of Surgery, St. Luke's Roosevelt Hospital, New York, NY, United States
| | - Dipali Sharma
- Department of Oncology, Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, United States
| | - Dong M Shin
- Winship Cancer Institute of Emory University, Atlanta, GA, United States
| | - David Sidransky
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Markus David Siegelin
- Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, United States
| | - Emanuela Signori
- National Research Council, Institute of Translational Pharmacology, Rome, Italy
| | - Neetu Singh
- Advanced Molecular Science Research Centre (Centre for Advanced Research), King George's Medical University, Lucknow, Uttar Pradesh, India
| | - Sharanya Sivanand
- Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Daniel Sliva
- DSTest Laboratories, Purdue Research Park, Indianapolis, IN, United States
| | - Carl Smythe
- Department of Biomedical Science, Sheffield Cancer Research Centre, University of Sheffield, Sheffield, United Kingdom
| | - Carmela Spagnuolo
- Institute of Food Sciences National Research Council, Avellino, Italy
| | - Diana M Stafforini
- Huntsman Cancer Institute and Department of Internal Medicine, University of Utah, Salt Lake City, UT, United States
| | - John Stagg
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Faculté de Pharmacie et Institut du Cancer de Montréal, Montréal, Quebec, Canada
| | - Pochi R Subbarayan
- Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Tabetha Sundin
- Department of Molecular Diagnostics, Sentara Healthcare, Norfolk, VA, United States
| | - Wamidh H Talib
- Department of Clinical Pharmacy and Therapeutics, Applied Science University, Amman, Jordan
| | - Sarah K Thompson
- Department of Surgery, Royal Adelaide Hospital, Adelaide, Australia
| | - Phuoc T Tran
- Departments of Radiation Oncology & Molecular Radiation Sciences, Oncology and Urology, Johns Hopkins School of Medicine, Baltimore, MD, United States
| | - Hendrik Ungefroren
- First Department of Medicine, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Matthew G Vander Heiden
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States
| | - Vasundara Venkateswaran
- Department of Surgery, University of Toronto, Division of Urology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Dass S Vinay
- Section of Clinical Immunology, Allergy, and Rheumatology, Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA, United States
| | - Panagiotis J Vlachostergios
- Department of Internal Medicine, New York University Lutheran Medical Center, Brooklyn, New York, NY, United States
| | - Zongwei Wang
- Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Kathryn E Wellen
- Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Richard L Whelan
- Department of Surgery, St. Luke's Roosevelt Hospital, New York, NY, United States
| | - Eddy S Yang
- Department of Radiation Oncology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, United States
| | - Huanjie Yang
- The School of Life Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang, China
| | - Xujuan Yang
- University of Illinois at Urbana Champaign, Champaign, IL, United States
| | - Paul Yaswen
- Life Sciences Division, Lawrence Berkeley National Lab, Berkeley, CA, United States
| | - Clement Yedjou
- Department of Biology, Jackson State University, Jackson, MS, United States
| | - Xin Yin
- Medicine and Research Services, Veterans Affairs San Diego Healthcare System & University of California, San Diego, CA, United States
| | - Jiyue Zhu
- Washington State University College of Pharmacy, Spokane, WA, United States
| | - Massimo Zollo
- Centro di Ingegneria Genetica e Biotecnologia Avanzate, Naples, Italy; Department of Molecular Medicine and Medical Biotechnology, Federico II, Via Pansini 5, 80131 Naples, Italy
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Shantha Kumara HMC, Gaita D, Miyagaki H, Yan X, Hearth SAC, Njoh L, Cekic V, Whelan RL. Plasma chitinase 3-like 1 is persistently elevated during first month after minimally invasive colorectal cancer resection. World J Gastrointest Oncol 2016; 8:607-614. [PMID: 27574553 PMCID: PMC4980651 DOI: 10.4251/wjgo.v8.i8.607] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2015] [Revised: 03/03/2016] [Accepted: 06/03/2016] [Indexed: 02/05/2023] Open
Abstract
AIM: To assess blood chitinase 3-like 1 (CHi3L1) levels for 2 mo after minimally invasive colorectal resection (MICR) for colorectal cancer (CRC).
METHODS: CRC patients in an Institutional Review Board approved data/plasma bank who underwent elective MICR for whom preoperative (PreOp), early postoperative (PostOp), and 1 or more late PostOp samples [postoperative day (POD) 7-27] available were included. Plasma CHi3L1 levels (ng/mL) were determined in duplicate by enzyme linked immunosorbent assay.
RESULTS: PreOp and PostOp plasma sample were available for 80 MICR cancer patients for the study. The median PreOp CHi3L1 level was 56.8 CI: 41.9-78.6 ng/mL (n = 80). Significantly elevated (P < 0.001) median plasma levels (ng/mL) over PreOp levels were detected on POD1 (667.7 CI: 495.7, 771.7; n = 79), POD 3 (132.6 CI: 95.5, 173.7; n = 76), POD7-13 (96.4 CI: 67.7, 136.9; n = 62), POD14-20 (101.4 CI: 80.7, 287.4; n = 22), and POD 21-27 (98.1 CI: 66.8, 137.4; n = 20, P = 0.001). No significant difference in plasma levels were noted on POD27-41.
CONCLUSION: Plasma CHi3L1 levels were significantly elevated for one month after MICR. Persistently elevated plasma CHi3L1 may support the growth of residual tumor and metastasis.
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Belizon A, Kirman I, Karten M, Jain S, Whelan RL. Rapid Increase in Serum Levels of Matrix Metalloproteinase-9 (MMP-9) Postoperatively is Associated With a Decrease in the Amount of Intracellular MMP-9. Surg Innov 2016; 12:333-7. [PMID: 16424954 DOI: 10.1177/155335060501200408] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
We have previously demonstrated a significant decrease in the serum concentration of intact insulin-like growth factor-binding protein (IGFBP-3) after laparotomy. IGFBP-3, a major IGF binding protein, inhibits the growth of tumor cells via several mechanisms. Our goal was to determine, in a murine model, whether matrix metalloproteinase-9 (MMP-9), a known protease of IGFBP-3, is responsible for the postoperative decrease in serum IGFBP-3 levels. Six IGFBP-3 transgenic mice on a CD-1 background were used in this study. These mice over-express human IGFBP-3. Sham laparotomy, in the form of a midline abdominal incision, was the test procedure. General anesthesia was established using ketamine and xylazine immediately before a 30-minute sham laparotomy and before preoperative blood sampling, done via retro-orbital venipuncture, 48 hours before surgery. The animals were sacrificed and blood was drawn 24 hours postoperatively. Plasma MMP-9 activity was measured using zymography at each time point (48 hours before and 24 hours after operation). MMP-9 activity was also measured in mononuclear cell lysates at both time points. Zymography analysis demonstrated significantly higher plasma levels of MMP-9 postoperatively compared with preoperative levels (81 RU vs 40 RU; P < .05). In contrast, mononuclear cell levels of MMP-9 were significantly higher preoperatively compared with postoperative levels (37.5 RU vs. 0.75 RU, P < .05). Plasma levels of MMP-9, a known protease of IGFBP-3, are significantly elevated postoperatively. In addition, mononuclear cells that store MMP-9 are depleted of it postoperatively. This suggests that rapid MMP-9 release by mononuclear cells leads to an increase in serum levels of this protease postoperatively. Further studies will elucidate mechanisms of MMP-9–related IGFBP-3 depletion.
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Affiliation(s)
- Avraham Belizon
- Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
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Manvelyan V, Khemarangsan V, Huang KG, Adlan AS, Lee CL. Port-site metastasis in laparoscopic gynecological oncology surgery: An overview. Gynecol Minim Invasive Ther 2016. [DOI: 10.1016/j.gmit.2015.06.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Kumara HMCS, Myers EA, Herath SAC, Jang JH, Njoh L, Yan X, Kirchoff D, Cekic V, Luchtefeld M, Whelan RL. Plasma monocyte chemotactic protein-1 remains elevated after minimally invasive colorectal cancer resection. World J Gastrointest Oncol 2014; 6:413-419. [PMID: 25320658 PMCID: PMC4197433 DOI: 10.4251/wjgo.v6.i10.413] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Revised: 08/20/2014] [Accepted: 09/17/2014] [Indexed: 02/05/2023] Open
Abstract
AIM: To investigate plasma Monocyte Chemotactic Protein-1 levels preoperatively in colorectal cancer (CRC) and benign patients and postoperatively after CRC resection.
METHODS: A plasma bank was screened for minimally invasive colorectal cancer resection (MICR) for CRC and benign disease (BEN) patients for whom preoperative, early postoperative, and 1 or more late postoperative samples (postoperative day 7-27) were available. Monocyte chemotactic protein-1 (MCP-1) levels (pg/mL) were determined via enzyme linked immuno-absorbent assay.
RESULTS: One hundred and two CRC and 86 BEN patients were studied. The CRC patient’s median preoperative MCP-1 level (283.1, CI: 256.0, 294.3) was higher than the BEN group level (227.5, CI: 200.2, 245.2; P = 0.0004). Vs CRC preoperative levels, elevated MCP-1 plasma levels were found on postoperative day 1 (446.3, CI: 418.0, 520.1), postoperative day 3 (342.7, CI: 320.4, 377.4), postoperative day 7-13 (326.5, CI: 299.4, 354.1), postoperative day 14-20 (361.6, CI: 287.8, 407.9), and postoperative day 21-27 (318.1, CI: 287.2, 371.6; P < 0.001 for all).
CONCLUSION: Preoperative MCP-1 levels were higher in CRC patients (vs BEN). After MICR for CRC, MCP-1 levels were elevated for 1 mo and may promote angiogenesis, cancer recurrence and metastasis.
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Comparison of hand-assisted laparoscopic surgery using tissue fusion devices and open resection for treatment of rectosigmoid carcinoma. Surg Laparosc Endosc Percutan Tech 2014; 24:e157-61. [PMID: 25090290 DOI: 10.1097/sle.0b013e3182a2b03e] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Modern tissue fusion devices used in hand-assisted laparoscopic surgery (HALS), a method of combining endoscopic surgery with tactile sensation, can minimize surgical trauma and hospitalization times beyond both conventional laparoscopy and open surgery. The outcomes of HALS using tissue fusion devices and conventional open surgery for curative resection of rectosigmoid carcinoma were compared. A total of 78 (45 males, 33 females; mean age, 57.2±11.7 y) rectosigmoid carcinoma patients underwent HALS surgery (HALS group) and 78 age-matched, sex-matched, and tumor status-matched rectosigmoid carcinoma patients (control group) underwent open resection between June 2008 and June 2010. In the HALS and control groups, abdominal incision length, intraoperative blood loss, procedure time, postoperative abdominal drainage, time to first flatus (bowel function return), length of hospital stay, morbidity, mortality, and pathology were assessed. Procedure times were similar in both groups (142.37±42.09 vs. 137.56±36.24 min). However, length of abdominal incision (5.14±0.47 vs. 13.17±2.41 cm), intraoperative blood loss (125.96±75.58 vs. 142.56±65.37 mL), need for postoperative analgesia, bowel function return (68.01±22.64 vs. 79.77±19.94 h), and postoperative hospital stay (6.47±1.73 vs. 7.73±1.71 d) were all significantly improved in the HALS group. At a median follow-up of 26 months, no significant differences in anastomotic recurrence were observed between groups (1 case/each group). Thus, the HALS approach for curative resection of rectosigmoid carcinoma was found to be similarly safe and effective compared with open resection. Furthermore, HALS may improve postoperative recovery and reduce hospitalization times.
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Jiang GQ, Chen P, Qian JJ, Yao J, Wang XD, Jin SJ, Bai DS. Perioperative advantages of modified laparoscopic vs open splenectomy and azygoportal disconnection. World J Gastroenterol 2014; 20:9146-9153. [PMID: 25083088 PMCID: PMC4112867 DOI: 10.3748/wjg.v20.i27.9146] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Revised: 03/16/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate perioperative outcomes in patients undergoing modified laparoscopic splenectomy or open splenectomy and azygoportal disconnection for portal hypertension.
METHODS: This study included 44 patients who underwent modified laparoscopic splenectomy and azygoportal disconnection (MLSD) and 71 who underwent open procedures for portal hypertension. Blood samples were collected before surgery and on days 1, 3, and 7 after surgery. Markers of liver and renal function, C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) were measured, and perioperative variables were compared between the two groups.
RESULTS: The modified laparoscopic group showed significantly better and faster recovery, better liver and renal function, and fewer complications than the open group. CRP, IL-6, and PCT concentrations on postoperative days 1, 3, and 7 were significantly lower in the modified laparoscopic group than in the open group.
CONCLUSION: MLSD was associated with lower inflammatory immune responses, less impairment of liver and renal function, and faster and better recovery.
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Minimally invasive colorectal resection is associated with significantly elevated levels of plasma matrix metalloproteinase 3 (MMP-3) during the first month after surgery which may promote the growth of residual metastases. Surg Endosc 2014; 28:3322-8. [PMID: 24939159 DOI: 10.1007/s00464-014-3612-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2014] [Accepted: 05/09/2014] [Indexed: 12/16/2022]
Abstract
INTRODUCTION MMP-3, a member of the matrix metalloproteinase (MMP) family, is involved in the breakdown of the extracellular matrix in tissue remodeling and may also play a role in cancer progression and metastasis. Minimally invasive colorectal resection (MICR) may increase plasma MMP-3 levels directly via surgical trauma or indirectly due to surgery-associated elevations in TNF-α and IL1 which are regulators of MMP-3. This study's purpose was to evaluate plasma MMP-3 levels during the first month after MICR for colorectal cancer. METHODS Patients enrolled in an IRB approved data/plasma bank who underwent elective MICR for CRC. Blood plasma samples had been collected preoperatively, on postoperative day (POD) 1, 3 and at varying postoperative time points and were stored at -80 °C. The late samples (POD 7-41) were bundled into 7 day time blocks and considered as single time points. MMP-3 levels were analyzed in duplicate via ELISA and the results reported as mean ± SD. The paired t test was used for analysis (significance, p < 0.008 after Bonferroni's correction). RESULTS A total of 73 CRC patients who underwent MICR met the inclusion criteria. The mean PreOp MMP-3 level was 14.9 ± 7.8 ng/ml (n = 73). Significantly elevated mean plasma levels were noted on POD 1 (21.4 ± 14.7 ng/ml, n = 73, p < 0.0001), POD 3 (37.9 ± 21.5 ng/ml, n = 72, p < 0.0001), POD 7-13 (22.0 ± 13.0 ng/ml, n = 56, p < 0.0001), POD 14-20 (21.9 ± 10.3 ng/ml, n = 20, p = 0.003), and on POD 21-27 (21.9 ± 11.43 ng/ml, n = 20, p = 0.002) when compared to PreOp levels. Plasma levels returned to the PreOp baseline at the POD 28-41 time point (n = 16, p = 0.07). CONCLUSION Plasma MMP-3 levels remained significantly elevated from baseline for 4 weeks after MICR for CRC. The early postoperative increase in MMP-3 levels may be due to the surgery-related acute inflammatory response; the elevation noted during weeks 2-3 may be related to wound healing. Increased MMP-3 levels may promote metastases or the growth of residual cancer.
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Karanika S, Karantanos T, Theodoropoulos GE. Immune response after laparoscopic colectomy for cancer: a review. Gastroenterol Rep (Oxf) 2013; 1:85-94. [PMID: 24759813 PMCID: PMC3938011 DOI: 10.1093/gastro/got014] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Background and aim: Colorectal cancer (CRC) is the third leading cause of cancer mortality worldwide and laparoscopic colectomy has been established as equivalent to the open approach in terms of oncological results and patients’ safety. Survival benefits have been reported in favor of laparoscopic colectomy (LC) in stage III CRC patients. Different immune responses after surgery, in terms of innate and cellular immunity, may potentially explain some of the reported differences. This review summarizes the literature on differences in immune response after the laparoscopic and the open approach for CRC. Materials and Methods: A literature search of electronic databases was conducted and all studies published on ‘colorectal cancer’, ‘laparoscopic and open colectomy’ ‘immune response’ and ‘surgical stress laparoscopy versus open’ were collected. Among these, the ones referring to CRC and those that had any clinical relevance offering information on perioperative parameters were used. Results: Despite the heterogeneity of studies, they support the view that innate immune response is activated to a greater degree in open colectomy (OC), which may be related to the more extensive trauma and surgical stress. On the other hand, cellular immunity is better preserved after LC. These differences are more pronounced in the immediate postoperative period. Conclusions: LC has been related to decreased up-regulation of innate immunity and better-preserved cellular immunity. The latter may be related to better anti-tumor activity and may be beneficial in terms of oncological survival in a subgroup of LC patients.
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Affiliation(s)
| | | | - George E. Theodoropoulos
- *Corresponding author. Asst. Professor of Surgery, Athens Medical School, 7 Semitelou Street, GR-11528 Athens, Greece. Tel: +30 6945463593; Fax: +30 2107707574; E-mail:
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Anwar S, Peter MB, Dent J, Scott NA. Palliative excisional surgery for primary colorectal cancer in patients with incurable metastatic disease. Is there a survival benefit? A systematic review. Colorectal Dis 2012; 14:920-30. [PMID: 21899714 DOI: 10.1111/j.1463-1318.2011.02817.x] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
AIM Patients with stage IV colorectal cancer with unresectable metastases can either receive chemotherapy or palliative resection of the primary lesion. In the absence of any randomized data the choice of initial treatment in stage IV colorectal cancer is not based on firm evidence. METHOD A search of MEDLINE, Pubmed, Embase and the Cochrane Library database was performed from 1980 to 2010 for studies comparing palliative resection in stage IV colorectal cancer with other treatment modalities. Audits and observational studies were excluded. Median survival was the primary outcome measure. The morbidity and mortality of surgical and nonsurgical treatments were compared. RESULTS Twenty-one studies (no randomized controlled trials) were identified. Most demonstrated a survival benefit for patients who underwent palliative resection. Multivariate analysis indicates that tumour burden and performance status are both major independent prognostic variables. Selection bias, incomplete follow up and nonstandardized reporting of complications make the data difficult to interpret. CONCLUSION The studies indicate that there may be a survival benefit for primary resection of colorectal cancer in stage IV disease. The findings suggest that resection of the primary tumour should be based on tumour burden and performance status rather than on the presence or absence of symptoms alone.
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Affiliation(s)
- S Anwar
- Department of Colorectal Surgery, Calderdale and Huddersfield NHS Trust, Huddersfield, UK.
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Shantha Kumara HMC, Kirchoff D, Herath SA, Jang JH, Yan X, Grieco M, Cekic V, Whelan RL. Plasma levels of angiopoietin-like protein 4 (ANGPTL4) are significantly lower preoperatively in colorectal cancer patients than in cancer-free patients and are further decreased during the first month after minimally invasive colorectal resection. Surg Endosc 2012; 26:2751-7. [PMID: 22549372 DOI: 10.1007/s00464-012-2269-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2011] [Accepted: 03/24/2012] [Indexed: 11/24/2022]
Abstract
BACKGROUND Surgery has been associated with proangiogenic plasma protein changes that may promote tumor growth. Angiopoietin-like protein 4 (ANGPTL4) is expressed by endothelial cells and other tissues in response to hypoxia. Both intact ANGPTL4 and its partly degraded C-terminal fragment may promote tumor angiogenesis. This study had two purposes: to measure and compare preoperative plasma ANGPTL4 levels in patients with colorectal cancer (CRC) and benign colorectal disease (BCD) and to determine plasma levels after minimally invasive colorectal resection (MICR) for CRC. METHODS Plasma was obtained from an IRB-approved plasma/data bank. Preoperative plasma ANGPTL4 levels were measured for CRC and BCD patients, but postoperative levels were determined only for CRC patients for whom a preoperative, a postoperative day (POD) 3, and at least one late postoperative sample (POD 7-55) were available. Late samples were bundled into four time blocks and considered as single time points. ANGPTL4 levels (mean ± SD) were measured via ELISA and compared (significance, p < 0.01 after Bonferroni correction). RESULTS Eighty CRC (71 % colon, 29 % rectal) and 60 BCD (62 % diverticulitis, 38 % adenoma) patients were studied. The mean preoperative plasma ANGPTL4 level in CRC patients (247.2 ± 230.7 ng/ml) was lower than the BCD group result (330.8 ± 239.0 ng/ml, p = 0.01). There was an inverse relationship between plasma levels and advanced CRC as judged by three criteria. In regard to the postoperative CRC analysis, the "n" for each time point varied: lower plasma levels (p < 0.001) were noted on POD 3 (161.4 ± 140.4 ng/ml, n = 80), POD 7-13 (144.6 ± 134.5 ng/ml, n = 46), POD 14-20 (139.0 ± 117.8 ng/ml, n = 27), POD 21-27 (138.9 ± 202.4, n = 20), and POD 28-55 (160.1 ± 179.0, n = 42) when compared to preoperative results. CONCLUSION CRC is associated with lower preoperative plasma ANGPTL4 levels compared with BCD, and the levels may vary inversely with disease severity. After MICR for CRC, levels are significantly lower for over a month compared with the preoperative level; the cause for this persistent decrease is unclear. The implications of both the lower preoperative level and the persistently decreased postoperative levels are unclear. Further studies are needed.
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Affiliation(s)
- H M C Shantha Kumara
- Division of Colon and Rectal Surgery, Department of Surgery, St Luke-Roosevelt Hospital Center, Suite 7B, 425 West, 59th Street, New York, NY 10019, USA.
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Yan X, Gardner TR, Grieco M, Herath SAC, Jang JH, Kirchoff D, Njoh L, Shantha Kumara HMC, Naffouje S, Whelan RL. Perioperative polyphenon E- and siliphos-inhibited colorectal tumor growth and metastases without impairment of gastric or abdominal wound healing in mouse models. Surg Endosc 2012; 26:1856-64. [PMID: 22258296 DOI: 10.1007/s00464-011-2114-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2011] [Accepted: 11/14/2011] [Indexed: 01/17/2023]
Abstract
INTRODUCTION Perioperative anticancer therapy that does not impair wound healing is needed to counter the persistent proangiogenic plasma compositional changes that occur after colorectal resection. Polyphenon E (PolyE), a green tea derivative (main component EGCG), and Siliphos (main component silibinin), from the milk thistle plant, both have antitumor effects. This study assessed the impact of PolyE/Siliphos (PES) on wound healing and the growth of CT-26 colon cancer in several murine models. METHODS One wound healing and three tumor studies were performed. Tumor Study (TS)1 assessed the impact of PES on subcutaneous tumor growth, whereas TS2 assessed PES's impact on subcutaneous growth when given pre- and post-CO(2) pneumoperitoneum (pneumo), sham laparotomy, or anesthesia alone. TS3 determined the ability of PES to limit hepatic metastases (mets) after portal venous injection of tumor cells. In the final study, laparotomy and gastrotomy wound healing were assessed several ways. BALB/c mice were used for all studies. The drugs were given via drinking water (PolyE) and gavage (Siliphos), daily, for 7-9 days preprocedure and for 7-21 days postoperatively. Tumor mass, number/size of hepatic mets, and proliferation and apoptosis rates were assessed. The abdominal breaking strength and energy to failure were measured postmortem as was gastric bursting pressures. RESULTS PES significantly inhibited subcutaneous growth in the nonoperative setting. PES also significantly decreased the number/size of liver mets when given perioperatively. Abdominal wound breaking strength, energy to wound failure, and collagen content were not altered by PES; gastrotomy bursting strength also was not affected by PES. Neither drug alone had a significant impact on tumor growth. CONCLUSIONS The PES combination inhibited subcutaneous and hepatic tumor growth yet did not impair wound healing. PES holds promise as a perioperative anticancer therapy.
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Affiliation(s)
- Xiaohong Yan
- Colon & Rectum Surgery, St. Luke's Roosevelt Hospital Center, 432 West, 58th Street, Room 517, New York, NY 10019, USA.
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Abstract
The rapid in development of surgical technology has had a major effect in surgical treatment of colorectal cancer. Laparoscopic colon cancer surgery has been proven to provide better short-term clinical and oncologic outcomes. However this quickly accepted surgical approach is still performed by a minority of colorectal surgeons. The more technically challenging procedure of laparoscopic rectal cancer surgery is also on its way to demonstrating perhaps similar short-term benefits. This article reviews current evidences of both short-term and long-term outcomes of laparoscopic colorectal cancer surgery, including the overall costs comparison between laparoscopic surgery and conventional open surgery. In addition, different surgical techniques for laparoscopic colon and rectal cancer are compared. Also the relevant future challenge of colorectal cancer robotic surgery is reviewed.
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Toll-like receptors in the inflammatory response during open and laparoscopic colectomy for colorectal cancer. Surg Endosc 2011; 26:330-6. [PMID: 21898023 DOI: 10.1007/s00464-011-1871-2] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2011] [Accepted: 07/25/2011] [Indexed: 12/12/2022]
Abstract
BACKGROUND Surgical interventions activate a cascade of reactions that result in an aseptic inflammatory reaction. This inflammatory response initiates the organism's innate immunity. Laparoscopic surgery reduces the trauma, and patients benefit from diminished surgical trauma and maintained immune function. Cytokine levels and C-reactive protein (CRP) are related to the magnitude of surgical trauma and surgical stress. Toll-like receptors (TLRs) 2 and 4 are the first sensor-recognition receptors of the invading pathogens for the innate immune response. This study aimed to compare the inflammatory response and then the stress response during laparoscopic and open colectomy for cancer by calculating TLR-2 and TLR-4 as the first sensor-recognition receptors together with interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitivity CRP (hsCRP). METHODS A total 40 patients with colorectal cancer were randomized in two groups: group A (open colectomy, n = 20) and group B (laparoscopic colectomy, n = 20). An epidural catheter was placed in all patients 1 h preoperatively. Rupivocaine was administered perioperatively and 48 h postoperatively. Blood samples were taken for calculation of IL-6, TNF-α, hsCRP, TLR-2, and TLR-4 preoperatively and 5 min after deflation of pneumoperitoneum (group B) or 5 min after division of the colon (group A), then 6 and 24 h postoperatively. RESULTS The mean operative time was 115 for group A and 142 min for group B. The mean blood loss was respectively 240 and 105 ml (P < 0.001), and the mean hospital stay was respectively 8 and 5 days (P < 0.05). The IL-6 level was significant higher in group A than in group B at 6 and 24 h postoperatively (P < 0.0001), and the hsCRP level was significant higher in group A than in group B at 24 h postoperatively (P < 0.001). The TNF-α values did not differ between the two groups. The TLR-2 level was significantly higher in group A than in group B at 5 min (P = 0.013) and 24 h (P = 0.007) postoperatively. The TLR-4 level was significant higher in group A than in group B at 5 min postoperatively (P = 0.03). CONCLUSION The inflammatory response and the resultant stress response are significantly less during laparoscopic colectomy than during open colectomy for colorectal cancer. This is an obvious short-term clinical benefit for the patient, providing tinder for further study to investigate the long-term results of laparoscopic colectomy versus open colectomy for colorectal cancer.
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Abstract
After over a decade of debate and controversy, it is now well established that laparoscopic colon surgery for cancer when compared with open surgery, results in short-term benefits while maintaining at least equivalent long-term outcomes. Consequently, more and more patients are undergoing laparoscopic colon surgery, but the adoption rate still remains relatively low in the United States. Similarly, there are many potential benefits to performing rectal surgery laparoscopically. Although not well documented, laparoscopic rectal surgery is under active investigation and may result in the usual short-term benefits associated with laparoscopic surgery. In this article, short- and long-term outcomes of patients undergoing laparoscopic colorectal surgery for cancer are reviewed. In addition, different technical options for laparoscopic approaches to colon and rectal cancer are compared.
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Affiliation(s)
- Sang W Lee
- Division of Colon and Rectal Surgery, New York Presbyterian Hospital, Weill-Cornell Medical College, New York, New York
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α-Defensin Expression of Inflammatory Response in Open and Laparoscopic Colectomy for Colorectal Cancer. World J Surg 2011; 35:1911-7. [DOI: 10.1007/s00268-011-1140-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Hou CY, Li XL, Jiang F, Gong RJ, Guo XY, Yao YQ. Comparative evaluation of surgical stress of laparoscopically assisted vaginal radical hysterectomy and lymphadenectomy and laparotomy for early-stage cervical cancer. Oncol Lett 2011; 2:747-752. [PMID: 22848260 DOI: 10.3892/ol.2011.311] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2010] [Accepted: 05/04/2011] [Indexed: 01/10/2023] Open
Abstract
The aim of this study was to objectively evaluate the benefits of laparoscopically assisted vaginal radical hysterectomy and lymphadenectomy for early-stage cervical cancer. Clinical data were prospectively collected from patients with IA-IIB cervical cancer who underwent laparoscopically assisted vaginal radical hysterectomy (n1=33) and laparotomy (n2=30). Peripheral blood samples were obtained prior to surgery and at 1 and 2 h into the operation, as well as on days 1, 4 and 7 following surgery to measure serum interleukin-6, C-reaction protein and cortisol. Results showed that there was no conversion to laparotomy in the laparoscopy group. The average blood loss was 317.23±217.20 ml (laparoscopy group) and 872.58±693.16 ml (laparotomy group). No significant difference was found in the number of resected pelvic lymph nodes (19.74±7.43 in the laparoscopy group and 20.35±6.62 in the laparotomy group). At days 1 and 7 after surgery, the serum IL-6 level was significantly different in the laparoscopy and laparotomy groups (day 1: laparoscopy group 17.14±16.53 pg/ml and laparotomy group 34.32±20.97 pg/ml, p=0.001; day 7: laparoscopy group 6.7±7.21 pg/ml and laparotomy group 17.54±16.47 pg/ml, p=0.001). The serum CRP level was significantly different at days 1 and 7 after the operation (day 1: laparoscopy group 7024.72±949.12 ng/ml and laparotomy group 7586.61±869.42 ng/ml, p=0.018; day 7: laparoscopy group 4357.71±2108.85 ng/ml and laparotomy group 6967.96±995.02 ng/ml, p<0.001). A significant difference was noted in the serum cortisol level at day 4 after the operation (122.29±65.17 ng/ml in the laparoscopy group and 186.76±68.61 ng/ml in the laparotomy group, p<0.001). In conclusion, the differences in clinical data and the various parameters pertinent to surgical stress evaluated in this study suggest that laparoscopic surgery for cervical cancer causes less postoperative stress than conventional open surgery.
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Affiliation(s)
- Cai-Ying Hou
- Department of Gynecology and Obstetrics, PLA General Hospital, Beijing 100853
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Lee SW, Whelan RL. Immunologic and oncologic implications of laparoscopic surgery: what is the latest? Clin Colon Rectal Surg 2010; 19:5-12. [PMID: 20011447 DOI: 10.1055/s-2006-939525] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Laparoscopic surgery has been associated with many short-term benefits such as a shorter time to recovery, return of bowel function, less pain, and a decrease in wound infection rate. Several animal and human experiments have demonstrated an immunologic and oncologic benefit of minimally invasive surgery. Whether these results will translate into similar results in human settings is unclear. Although the first published prospective randomized clinical trial suggests better long-term outcomes for patients undergoing laparoscopic surgery, results from other ongoing randomized, controlled clinical trials are needed to verify this controversial result.
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Affiliation(s)
- Sang W Lee
- Department of Surgery, New York Presbyterian Hospital, Weill Medical College of Cornell University, New York, NY 10021, USA.
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Schillaci G, Rondelli F, Pirro M, Bagaglia F, Pucci G, Noya G, Mannarino E. Endothelial progenitor cells are mobilized after major laparotomic surgery in patients with cancer. Int J Immunopathol Pharmacol 2010; 22:1035-41. [PMID: 20074467 DOI: 10.1177/039463200902200419] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The progression of cancer is largely dependent on neoangiogenesis. Circulating endothelial progenitor cells (EPC) have the ability to form complete vascular structures in vitro and play a crucial role in tumor vasculogenesis. Emerging evidence suggests that surgical injury may induce the mobilization of EPC in animal models, and this might have a negative effect on the prognosis of cancer patients. We studied 20 patients (10 men, 65+/-13 years) undergoing laparotomy for surgical treatment of various forms of abdominal cancer, and 20 age- and sex-matched healthy control subjects. The number of circulating EPC, defined as CD34+/KDR+ cells identified among mononuclear cells isolated from peripheral venous blood, was determined preoperatively and at days 1 and 2 after surgery. Surgery induced a significant increase in circulating EPC levels at day 1 (from 278/mL, interquartile range 171-334, to 558/mL, interquartile range 423-841, p<0.001) and day 2 (709/mL, interquartile range 355-834, p<0.001)compared with baseline values. EPC levels did not change in control subjects. Seven subjects who underwent laparotomic surgery for non-neoplastic disease also showed an increase in EPC levels after surgery (p=0.009 and p=0.028 at day 1 and day 2, respectively). We conclude that patients undergoing elective laparotomic surgery for cancer demonstrate an increase in EPC post-operatively. The potential adverse effects of surgical stress-induced EPC mobilization on tumor and metastasis growth in cancer patients need to be addressed in future studies.
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Affiliation(s)
- G Schillaci
- Unit of Internal Medicine, Angiology and Arteriosclerosis, University of Perugia, Perugia, Italy.
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Perry KA, Enestvedt CK, Hosack LW, Pham TH, Diggs BS, Teh S, Orloff S, Winn S, Hunter JG, Sheppard BC. Increased vascular endothelial growth factor transcription in residual hepatocellular carcinoma after open versus laparoscopic hepatectomy in a small animal model. Surg Endosc 2009; 24:1151-7. [DOI: 10.1007/s00464-009-0742-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2009] [Accepted: 10/09/2009] [Indexed: 12/27/2022]
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Donigan M, Loh BD, Norcross LS, Li S, Williamson PR, DeJesus S, Ferrara A, Gallagher JT, Baker CH. A metastatic colon cancer model using nonoperative transanal rectal injection. Surg Endosc 2009; 24:642-7. [PMID: 19688392 DOI: 10.1007/s00464-009-0650-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2009] [Revised: 06/24/2009] [Accepted: 07/16/2009] [Indexed: 12/22/2022]
Abstract
BACKGROUND This study aimed to develop a noninvasive orthotopic model for metastasis of colon and rectal cancer using a transanal approach. Currently, the most accurate orthotopic representation of metastatic human colon cancer is via a cecal injection. The transanal model allows for further examination of systemic immune responses, tumor take, and onset of metastasis without prior surgical intervention. METHODS For this study, 60 Balb/c mice were anesthetized and subjected to gentle anal dilation using blunt-tipped forceps at the anal opening. Murine colon cancer parental CT26 or luciferase-labeled CT26 (CT26-luc) cells were injected submucosally into the distal posterior rectum (30 CT26 and 30 CT26 injections) at concentrations of 2.5 x 10(4), 1 x 10(5), and 1 x 10(6) in a volume of 50 microl. Tumor growth and metastatic development was monitored at 5-day intervals for 50 days. All the remaining mice were killed on postinjection day 50. RESULTS The optimal concentration for metastasis and survival of the mice was 2.5 x 10(4) cells. Higher concentrations of cells yielded higher mortality but did not result in metastasis. The overall success of tumor growth in both experiments using the transanal rectal injection was 65%. Histology showed that all tumors were poorly differentiated adenocarcinomas. Two mice (3.3%) from the 2.5 x 10(4) CT26-luc group showed metastatic colonic adenocarcinoma to the liver on postinjection day 50. CONCLUSION Transanal rectal injection of colon cancer cells offers a nonoperative orthotopic murine model for colon cancer that may lead to the development of metastasis. By using an orthotopic model, more aspects of metastatic colon cancer can be evaluated without the influence of a previous abdominal incision. These results warrant more investigation.
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Affiliation(s)
- Melissa Donigan
- Cancer Research Institute of MD Anderson Cancer Center Orlando, 110 Bonnie Loch Court, Orlando, FL 32806, USA
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Donigan M, Norcross LS, Aversa J, Colon J, Smith J, Madero-Visbal R, Li S, McCollum N, Ferrara A, Gallagher JT, Baker CH. Novel murine model for colon cancer: non-operative trans-anal rectal injection. J Surg Res 2008; 154:299-303. [PMID: 19101690 DOI: 10.1016/j.jss.2008.05.028] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2008] [Revised: 05/16/2008] [Accepted: 05/21/2008] [Indexed: 02/06/2023]
Abstract
BACKGROUND This study was conducted to develop a modified murine model of colon cancer that is non-operative. Currently, the most accurate orthotopic murine model of colon cancer requires an invasive procedure involving cecal injection of colon cancer cells and therefore limits the ability to perform immunological studies subsequent to cecal resections. MATERIALS AND METHODS Murine colon cancer (CT26) cells were injected submucosally into the distal, posterior rectum of BALB/c mice. Care was taken not to pass transmurally into the pelvic cavity. Different magnifications (10x versus 100x) were used for injection, and primary tumor growth and metastatic disease were studied. RESULTS In the initial study, 3/7 mice injected using 10x magnifications had notable, large tumor originating from the rectal wall, and histology revealed that all excised tumors were poorly differentiated adenocarcinoma. In the second study, 8/10 mice injected using 100x magnifications had notable tumor originating from the rectal well, and 4/8 mice had abnormal lung tissue with pathological evidence of hemorrhagic pulmonary edema. The use of 10x magnification resulted in 43% tumor take. In sharp contrast, 80% tumor take was observed with 100x magnification. The overall success of tumor take was 65% using the trans-anal rectal injection model. CONCLUSIONS Our modified orthotopic murine model of colon cancer offers an alternative non-operative murine model for colon cancer and is less invasive than the traditional orthotopic model (i.e., cecal injection). This model may allow for more accurate investigations of inflammation and immune responses to surgical intervention without the influence of previous abdominal surgery.
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Affiliation(s)
- Melissa Donigan
- Cancer Research Institute of M. D. Anderson Cancer Center Orlando, Orlando, Florida 32806, USA
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Survival and symptomatic benefit from palliative primary tumor resection in patients with metastatic colorectal cancer: a review. Int J Colorectal Dis 2008; 23:559-68. [PMID: 18330581 DOI: 10.1007/s00384-008-0456-6] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/12/2008] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Patients with metastatic colorectal cancer have a limited life expectancy and are at risk for life-threatening tumor-related obstruction, perforation, and hemorrhage. Though surgical resection is performed frequently in this setting, its true benefit is not well-established. MATERIALS AND METHODS We reviewed the medical literature from 1996-2006 using the search terms metastatic colorectal cancer and primary resection to find studies that evaluated the management of primary tumors in metastatic colorectal cancer. All search results were included in our analysis and were assessed on the basis of methodologic quality. RESULTS/FINDINGS Twelve relevant studies were identified; ten were single-institution retrospective reviews and two were population-based studies using National Cancer Institute's Surveillance, Epidemiology, and End-Results database. No prospective or randomized studies were identified. Approximately 70% of patients diagnosed with metastatic colorectal cancer in the USA undergo primary tumor resection; only a minority have this done for tumor-related symptoms or as part of potentially curative resection. The postoperative mortality ranged from 9.0-11.2% in large cancer registries but was often lower in major cancer centers. Resection of asymptomatic primary tumors was frequently associated with prolonged survival but was not found to reduce significantly the incidence of life-threatening tumor-related complications. INTERPRETATION/CONCLUSION Retrospective data suggest that non-curative resection of asymptomatic colorectal primary tumors may prolong survival; however, selection bias and unaccounted clinical factors may explain this observation. Prospective, randomized surgical trials are needed to test the role of primary tumor resection in this setting, especially because of its current widespread use, and its associated cost, morbidity, and high postoperative mortality.
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Bourdel N, Matsuzaki S, Bazin JE, Darcha C, Pouly JL, Mage G, Canis M. Postoperative peritoneal dissemination of ovarian cancer cells is not promoted by carbon-dioxide pneumoperitoneum at low intraperitoneal pressure in a syngenic mouse laparoscopic model with controlled respiratory support: a pilot study. J Minim Invasive Gynecol 2008; 15:321-6. [PMID: 18439505 DOI: 10.1016/j.jmig.2008.02.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2007] [Revised: 02/04/2008] [Accepted: 02/08/2008] [Indexed: 11/30/2022]
Abstract
STUDY OBJECTIVE To investigate postoperative peritoneal dissemination of ovarian cancer cells in a syngenic mouse model with and without controlled respiratory support (CRS). DESIGN Randomized controlled trial (Canadian Task Force classification I). SETTING Academic facility. SUBJECTS Sixty-four female C57BJ6 mice. INTERVENTIONS Mice were randomly divided into 4 surgical groups: anesthesia alone group; 2 carbon-dioxide pneumoperitoneum groups, 1 with low (2 mm Hg) and 1 with high (8 mm Hg) intraperitoneal pressure (IPP); and finally the laparotomy group. Each of the 4 groups was then subdivided into one group with CRS and the other without. Mouse ovarian cancer cells were injected intraperitoneally just before surgery. MEASUREMENTS AND MAIN RESULTS A laparotomy was performed to evaluate postoperative peritoneal dissemination of ovarian cancer cells on postoperative day 14. A computerized analysis system was then used to evaluate peritoneal dissemination. In the groups with CRS, the peritoneal dissemination score was significantly higher in the laparotomy and high IPP groups compared with anesthesia alone (p <.0001 vs laparotomy, p <.002 vs high IPP) and low IPP (p <.0002 vs laparotomy, p <.004 vs high IPP) groups. No significant difference was detected between the low IPP and anesthesia alone groups. CONCLUSION Postoperative peritoneal dissemination of ovarian cancer cells is not promoted by a carbon-dioxide pneumoperitoneum with a low IPP in a mouse model with CRS when assessed on postoperative day 14.
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Affiliation(s)
- Nicolas Bourdel
- Université d'Auvergne-Clermont I, Centre d'Endoscopie et des Nouvelles Techniques Interventionnelles, Clermont-Ferrand, France
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CO2 pneumoperitoneum increases systemic but not local tumor spread after intraperitoneal murine neuroblastoma spillage in mice. Surg Endosc 2008; 22:2648-53. [DOI: 10.1007/s00464-008-9778-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2007] [Accepted: 10/15/2007] [Indexed: 10/22/2022]
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Belizon A, Balik E, Horst P, Feingold D, Arnell T, Azarani T, Cekic V, Skitt R, Kumara S, Whelan RL. Persistent elevation of plasma vascular endothelial growth factor levels during the first month after minimally invasive colorectal resection. Surg Endosc 2008; 22:287-97. [PMID: 18204877 DOI: 10.1007/s00464-007-9725-7] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2007] [Revised: 07/11/2007] [Accepted: 11/09/2007] [Indexed: 01/29/2023]
Abstract
BACKGROUND Elevations of plasma vascular endothelial growth factor (VEGF) have been noted early after colorectal resection. The duration of this increase is unknown. Because VEGF is a potent promoter of angiogenesis, which is critical to tumor growth, a sustained increase in blood VEGF levels after surgery may stimulate the growth of residual metastases early after surgery. This preliminary study aimed to determine VEGF levels during the first month after colorectal resection. METHODS Patients from three prospective studies that had late postoperative blood samples available comprised the study population. Demographic, perioperative, pathologic, and complication data were collected. Plasma samples were obtained preoperatively for all patients: on postoperative day (POD) 1 for most patients and at varying time points thereafter during the first month after surgery and beyond. Levels of VEGF were determined via enzyme-linked immunoassay (ELISA) and compared using Wilcoxon's matched pairs test. Because the numbers of specimens beyond POD 5 were limited, samples from 7-day time blocks were bundled and averaged to permit statistical analysis. RESULTS A total of 49 patients with cancer and 30 patients with benign indications, all of whom underwent minimally invasive colorectal resection, were assessed separately. With regard to the patients with cancer, the median preoperative plasma value was 150 pg/ml, and the peak postoperative median value for the POD 14 to 20 time block was 611.1 pg/ml. Furthermore, compared with the preoperative results, significant VEGF elevations were noted on POD 3 as well as during week 2 (POD 7-13), week 3 (POD 14-20), and week 4 (POD 21-27) (p < 0.05 for each). With regard to the benign patients, the median preoperative VEGF level was 112 pg/ml, and the peak postoperative value, 286 pg/ml, was noted during postoperative week 2. Significant elevations were noted on POD 3, and for weeks 2 and 3 as well as for POD 28 and later. Between 63% and 89% of the patients at each time point beyond POD 5 had elevated VEGF levels. CONCLUSION This preliminary study demonstrates that after minimally invasive colorectal resection for cancer, median VEGF levels are significantly elevated on POD 3 and remain increased for as long as 4 weeks. Significant elevations in a similar pattern also were noted for the benign patients. However, the baseline and postoperative median values were lower. The clinical impact from increased blood levels of VEGF is uncertain. It is possible that the growth of residual tumor deposits may be stimulated early after surgery. These results warrant a larger study as well as endothelial cell in vitro assays to determine whether postoperative plasma stimulates proliferation and invasion.
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Affiliation(s)
- A Belizon
- New York Presbyterian Hospital, Columbia University College of Physicians and Surgeons, New York, NY, USA.
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Kirman I, Belizon A, Balik E, Feingold D, Arnell T, Horst P, Kumara S, Cekic V, Jain S, Nasar A, Whelan RL. Perioperative sargramostim (recombinant human GM-CSF) induces an increase in the level of soluble VEGFR1 in colon cancer patients undergoing minimally invasive surgery. Eur J Surg Oncol 2007; 33:1169-76. [PMID: 17512160 DOI: 10.1016/j.ejso.2007.03.014] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2006] [Accepted: 03/16/2007] [Indexed: 11/21/2022] Open
Abstract
INTRODUCTION Experimentally, laparotomy is associated with increased tumor growth. In humans, abdominal surgery is associated with immunosuppression and elevated plasma VEGF levels that might stimulate tumor growth early after surgery. Avoidance of these surgery-related changes and their consequences may be advantageous. Granulocyte-macrophage colony stimulating factor (GMCSF) is a non-specific immune system up-regulator that has also been associated, experimentally, with increased release of soluble VEGF Receptor 1 (sVEGFR1) which is an endogenous inhibitor of VEGF. This study's purpose was to determine the impact of perioperatively administered recombinant human GMCSF (rhu-GMCSF) on both immune function and plasma sVEGFR1 levels in colorectal cancer patients. METHODS This randomized placebo-controlled study included 36 colorectal cancer patients who underwent minimally invasive resection (17 GMCSF, 19 Placebo). Patients received 7 subcutaneous injections of either rhu-GMCSF, 125 microg/m2, or saline on preoperative days 3, 2 and 1 and on postoperative days (POD) 1, 2, 3 and 4. A number of immune parameters were followed and plasma levels of soluble VEGF Receptor 1 (sVEGFR1) and VEGF were determined. RESULTS The total WBC, neutrophil, eosinophil, and monocyte counts were significantly higher after surgery in the GMCSF group; no differences were noted for the other immune parameters. In the GMCSF group, median plasma sVEGFR1 levels were significantly elevated on POD 1 (188.1 pg/ml), and on POD 5 (142.8 pg/ml) when compared to pre-GMCSF levels (0 pg/ml) (p-value<0.05 for all comparisons). In the placebo group, the POD5 median sVEGFR1 level (116.3 pg/ml) was elevated and of borderline significance (p=0.05) vs the pre-treatment result (0 pg/ml). Of note, both groups had significantly elevated median plasma VEGF levels on POD 5 (Control 435.7 pg/ml; GMCSF 385.3 pg/ml) when compared to their preoperative results (Control 183.3 pg/ml, p=0.0013; GMCSF 171.5 pg/ml, p=0.0055). CONCLUSIONS Perioperative GMCSF was not associated with an immune function benefit in this study, however, such treatment leads to increased plasma sVEGFR1 levels. Colorectal resection, with or without GMCSF, was also associated with increased VEGF levels postoperatively. Increased plasma levels of sVEGFR1 after surgery might limit the pro-angiogenic tumor stimulatory effects of VEGF. Further study of GMCSF's impact on angiogenesis appears warranted.
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Affiliation(s)
- I Kirman
- College of Physicians and Surgeons of Columbia University, Department of Surgery, 630 West 168th Street, New York, NY 10032, USA
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Allendorf J. Oncologic Impact of Surgery in the Early Postoperative Period. SEMINARS IN COLON AND RECTAL SURGERY 2007. [DOI: 10.1053/j.scrs.2007.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Sylla P. Microarray Studies of Immune Function After Surgery. SEMINARS IN COLON AND RECTAL SURGERY 2007. [DOI: 10.1053/j.scrs.2007.10.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Georges C, Lo T, Alkofer B, Whelan R, Allendorf J. The effects of surgical trauma on colorectal liver metastasis. Surg Endosc 2007; 21:1817-9. [PMID: 17522938 DOI: 10.1007/s00464-007-9290-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2007] [Revised: 01/09/2007] [Accepted: 02/06/2007] [Indexed: 10/23/2022]
Affiliation(s)
- C Georges
- Department of Surgey, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA.
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Belizon A, Kirman I, Balik E, Karten M, Jain S, Whelan RL. Major surgical trauma induces proteolysis of insulin-like growth factor binding protein-3 in transgenic mice and is associated with a rapid increase in circulating levels of matrix metalloproteinase-9. Surg Endosc 2006; 21:653-8. [PMID: 17165116 DOI: 10.1007/s00464-006-9103-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2006] [Accepted: 10/16/2006] [Indexed: 11/29/2022]
Abstract
BACKGROUND The authors previously demonstrated a significant decrease in plasma levels of intact insulin-like growth factor binding protein-3 (IGFBP-3) after major open but not after laparoscopic-assisted surgery in humans. They postulated that this decrease may have an effect on postoperative tumor growth. It also has been shown that plasma levels of matrix metalloproteinase-9 (MMP-9), a protease capable of degrading IGFBP-3, are transiently increased after open colectomy in humans. The authors aimed to develop an animal model that would allow further study of the effect that surgical trauma has on plasma levels IGFBP-3 and MMP-9. In addition, they set out to assess the concentration of MMP-9 in circulating monocytes before and after surgery. METHODS The 30 mice included in this study were divided into three groups: sham laparotomy, carbon dioxide (CO2) pneumoperitoneum, and anesthesia control. All mice were IGFBP-3 transgenics (overexpressing human IGFBP-3) on a CD1 background. The mice were anesthetized using ketamine and xylazine. Blood was drawn retroorbitally 48 h before the procedure. The duration of the procedure was 30 min. The animals were killed 24 h postoperatively and blood was drawn. Intact IGFBP-3 levels were measured using a combination of Western blot analysis and enzyme-linked immunoassay (ELISA) at the two time points: before and after the operation. Plasma and peripheral blood mononuclear cell levels of MMP-9 were measured at each time point using zymography. Mononuclear cell lysates were used to determine intracellular MMP-9 levels. RESULTS Plasma levels of intact IGFBP-3 were significantly lower than preoperative levels after sham laparotomy. A mean decrease of 76.6% was noted (p < 0.05). Zymography demonstrated significantly higher plasma MMP-9-related proteolytic activity than observed preoperatively after sham laparotomy (78.5 vs 42.3 Relative Units [RU]; p < 0.05). In the pneumoperitoneum group, no significant decrease was found between the pre- and postoperative levels of intact IGFBP-3. A nonsignificant increase in MMP-9 was noted after CO2 pneumoperitoneum (38 RU preoperatively vs. 46.4 RU postoperatively; p > 0.05). The anesthesia control group did not demonstrate a significant change in either circulating intact IGFBP-3 levels or MMP-9 levels. Mononuclear intracellular levels of MMP-9 were significantly lower after laparotomy than the preoperative levels (3 vs 37 RU). The postprocedure intracellular levels of MMP-9 were not significantly decreased in the pneumoperitoneum or anesthesia control group. CONCLUSION Plasma levels of intact IGFBP-3, a cell growth regulating factor, were found to be decreased significantly after laparotomy. This decrease was not seen after pneumoperitoneum. Depletion of intact IGFBP-3 after laparotomy correlated with a rapid release of MMP-9 from mononuclear cells and an increase in circulating plasma MMP-9 levels. Matrix metalloproteinase-9 may play an important role in IGFBP-3 proteolysis after surgical trauma. Furthermore, circulating mononuclear cells are one source of MMP-9 after surgery. Finally, the model used reproduces events in humans after surgery, and thus should permit further study on the mechanism of IGFBP-3 proteolysis after surgical trauma.
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Affiliation(s)
- A Belizon
- Section of Colon and Rectal Surgery, Columbia University Medical Center, 161 Ft. Washington Ave. 8th Floor, New York, NY 10032, USA
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Belizon A, Balik E, Feingold DL, Bessler M, Arnell TD, Forde KA, Horst PK, Jain S, Cekic V, Kirman I, Whelan RL. Major abdominal surgery increases plasma levels of vascular endothelial growth factor: open more so than minimally invasive methods. Ann Surg 2006; 244:792-8. [PMID: 17060773 PMCID: PMC1856599 DOI: 10.1097/01.sla.0000225272.52313.e2] [Citation(s) in RCA: 94] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
INTRODUCTION Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis that is necessary for wound healing and also promotes tumor growth. It is anticipated that plasma levels would increase after major surgery and that such elevations may facilitate tumor growth. This study's purpose was to determine plasma VEGF levels before and early after major open and minimally invasive abdominal surgery. METHODS Colorectal resection for cancer (n = 139) or benign pathology (n = 48) and gastric bypass for morbid obesity (n = 40) were assessed. Similar numbers of open and laparoscopic patients were studied for each indication. Plasma samples were obtained preoperatively and on postoperative days (POD) 1 and 3. VEGF levels were determined via ELISA. The following statistical methods were used: Fisher exact test, unmatched Student t test, Wilcoxon's matched pairs test, and the Mann Whitney U Test with P < 0.05 considered significant. RESULTS The mean preoperative VEGF level of the cancer patients was significantly higher than baseline level of benign colon patients. Regardless of indication or surgical method, on POD3, significantly elevated mean VEGF levels were noted for each subgroup. In addition, on POD1, open surgery patients for all 3 indications had significantly elevated VEGF levels; no POD1 differences were noted for the closed surgery patients. At each postoperative time point for each procedure and indication, the open group's VEGF levels were significantly higher than that of the matching laparoscopic group. VEGF elevations correlated with incision length for each indication. CONCLUSION As a group colon cancer patients prior to surgery have significantly higher mean VEGF levels than patients without tumors. Also, both open and closed colorectal resection and gastric bypass are associated with significantly elevated plasma VEGF levels early after surgery. This elevation is significantly greater and occurs earlier in open surgery patients. The duration and clinical importance of this finding is uncertain but merits further study.
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Affiliation(s)
- Avraham Belizon
- Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
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Abstract
OBJETIVO: O objetivo deste trabalho foi determinar a exeqüibilidade, reprodutibilidade e segurança da esplenectomia subtotal por via laparoscópica e suas repercussões morfológicas, hematológicas, imunitárias e de depuração sangüínea, comparando esses dados com os obtidos na esplenectomia laparotómica. MÉTODO: Este estudo experimental foi conduzido de acordo com os princípios éticos de pesquisa experimental, propostos pelo Comitê de Ética em Experimentação Animal da UFMG. Quatorze cães adultos mestiços de ambos os sexos foram distribuídos em dois grupos (n = 7): Grupo 1 - Esplenectomia subtotal laparoscópica, preservando o polo superior suprido exclusivamente pelos vasos esplenogástricos; a secção esplênica e hemostasia foram realizadas utilizando um grampeador linear cortante laparoscópico com carga de 45 mm de extensão. Grupo 2 - Esplenectomia total, realizada por meio de laparotomia mediana. Depois de três meses, foram analisadas as alterações nos exames hematológico, imunitário e cintilográfico em todos os animais. Secções dos remanescentes esplênicos, fígado e linfonodos foram avaliadas histologicamente. RESULTADOS: Todos os procedimentos transcorreram sem complicações, não havendo morte operatória e com perda sangüínea mínima. Todos os animais sobreviveram à operação durante os três meses de acompanhamento. Após esse período, houve redução da contagem de plaquetas (p < 0,05) no Grupo 1. O restante dos exames hematológicos permaneceu normal. Os remanescentes esplênicos apresentaram arquitetura semelhante ao baço normal. Não houve alterações histológicas nos linfonodos e fragmentos hepáticos. CONCLUSÕES: É possível e segura a realização da esplenectomia subtotal por via laparoscópica no cão.
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Delgado Gomis F, Gómez Abril SA, Martínez Abad M, Guallar Rovira JM. Assisted laparoscopic transhiatal esophagectomy for the treatment of esophageal cancer. Clin Transl Oncol 2006; 8:185-92. [PMID: 16648118 DOI: 10.1007/s12094-006-0009-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Esophageal resection for the treatment of esophageal cancer is usually associated with high morbido-mortality risks, that can be reduced using laparoscopy. Laparoscopic transhiatal esophagectomy (LTE) has the potential to improve these results but, to-date, only a few limited series of cases have been reported. This report summarizes our experience in 24 cases. OBJECTIVE To assess the outcomes following LTE. METHODS AND MATERIALS Between 1998 and 2005, LTE was performed in 24 patients; 18 men and 6 women with an overall mean age of 63 years (range: 36-85). Indication for surgery was lower third esophageal cancer; 11 squamous cell carcinoma and 13 adenocarcinoma. Neoadjuvant chemotherapy and radiotherapy were used in 18 patients (75%). A laparoscopic transhiatal approach was used to perform an esophagectomy with curative intent. A cervical esophagogastric anastomosis was created. RESULTS No reversion to conventional open surgery was required. Mean anesthesia time was 293.8 min (range: 255-360). Major complications occurred in 7 patients (29.2%). Two patients (8.3%) had leakage from the cervical anastomosis. Surgical mortality was 8.3%. The median stay in Intensive Care Unit was 5 days (range: 1-29). Median hospital stay was 11.5 days (range: 7-54). At a mean follow-up of 24.9 months, 8 patients (36.4%) had disease recurrence (36.4%), global survival rate was 62.5%, and diseasefree survival rate was 50%. CONCLUSIONS Assisted laparoscopic transhiatal esophagectomy for lower third esophageal cancer is a potentially safe and effective method when performed by surgeons with expertise in the field. Benefits from this approach need to be confirmed by further randomized studies.
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Affiliation(s)
- Fernando Delgado Gomis
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Dr. Peset, S.V.S. Valencia, Spain
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Carter JJ, Feingold DL, Wildbrett P, Oh A, Kirman I, Asi Z, Stapleton G, Huang E, Fine RL, Whelan RL. Significant reduction of laparotomy-associated lung metastases and subcutaneous tumors after perioperative immunomodulation with flt3 ligand in mice. Surg Innov 2006; 12:319-25. [PMID: 16424952 DOI: 10.1177/155335060501200406] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Laparotomy has been associated with increased rates of tumor establishment and metastasis formation postoperatively in animal models. The purpose of this study was to determine the impact on postoperative tumor growth of perioperative upregulation of immune function via fetal liver tyrosine kinase 3 (Flt3 ligand). Two murine studies were carried out: the first utilized a lung metastases model, and the second involved a subcutaneous tumor model. Each study included four groups: anesthesia control (AC), AC plus Flt3 ligand (ACFlt3), sham laparotomy (OP), and OP plus Flt3 ligand (OPFlt3). Flt3 ligand was administered by daily intraperitoneal injection (10 mug/dose) beginning 5 days preoperatively and continuing for 1 week postoperatively. In study 1, A/J mice were given tail vein injections of 1.5 x 10(5) TA3Ha cancer cells on the day of surgery. The mice were sacrificed 14 days after surgery, the lungs processed, and the surface metastases counted by a blinded observer. In study 2 C3H/He mice were given a dorsal subcutaneous injection of 10(4) MC-2 cancer cells on the day of surgery. The mice were sacrificed 31 days after surgery, and the injection sites were evaluated for subcutaneous tumors grossly and histologically. In study 1, the median number of surface lung metastases per mouse was 166 in the OP group and 38 in the OPFlt3 (P = .021). Mice in the AC group developed a median 50 lung metastases per animal compared with mice in the ACFlt3 group who had a median of 10 metastases per mouse (P = .001). The OP group had significantly more metastases than the AC group (P = .048). In study 2, the percentage of animals that developed tumors in the AC, OP, ACFlt3, and OPFlt3 groups was 43, 80, 0, and 20, respectively. The incidence of tumors in the OPFLt3 group and the ACFlt3 group was significantly less than their respective control groups (P < .01). The difference between the OP and AC groups was not significant (P > .05). Perioperatively administered Flt3 ligand was associated with significantly fewer lung metastases and a lower incidence of subcutaneous tumor formation after laparotomy and anesthesia alone. Perioperative immunomodulation may limit untoward surgery-related oncologic effects.
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Affiliation(s)
- Joseph J Carter
- Laparoscopic Physiology and Oncology Laboratory, Department of Surgery, College of Physician and Surgeons, Columbia University, New York, NY 10032, USA
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Kim JC, Kim HC, Lee KH, Yu CS, Kim TW, Chang HM, Ryu MH, Kim JH, Ha HK, Lee MG. Hepatic arterial infusion alternating with systemic chemotherapy in patients with non-resectable hepatic metastases from colorectal cancer. J Gastroenterol Hepatol 2006; 21:1026-35. [PMID: 16724990 DOI: 10.1111/j.1440-1746.2005.04023.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM Hepatic arterial infusion (HAI) chemotherapy has a number of limitations, including a low rate of complete response and frequent extrahepatic recurrence, in colorectal cancer patients with non-resectable hepatic metastases. METHODS Twenty-nine colorectal cancer patients with non-resectable hepatic metastases were consecutively enrolled for HAI alternating with systemic chemotherapy (HA + SC group). The protocol comprised six cycles of alternating HAI (5-FU + leucovorin for 14 days, and mitomycin C on the first day) and systemic chemotherapy (5-FU + leucovorin). Colorectal cancer patients with two or more hepatic metastases treated using hepatic resection and systemic chemotherapy (HR + SC group) were selected as a comparative group. RESULTS Within the HA + SC group, complete response was achieved in eight patients (28%), whereas 13 patients (45%) showed progressive disease. Six of the eight patients with complete response lived for more than 38 months. Extrahepatic recurrences were more frequent in the HR + SC group than the HA + SC group (47 vs 21%, P = 0.024). The two groups did not differ with respect to overall and hepatic progression-free survival (P = 0.947 and 0.444, respectively), displaying median +/- SE values of 38 +/- 7 and 20 +/- 3 months in the HA + SC group, and 39 +/- 9 and 33 +/- 14 months in the HR + SC group, respectively. One patient in each group experienced toxic hepatitis, and sclerosing cholangitis occurred in one patient of the HA + SC group. Other complications were mostly grade 1 or 2. CONCLUSIONS HAI alternating with systemic chemotherapy led to a promising response and hepatic progression-free survival, possibly reducing extrahepatic recurrence in colorectal cancer patients with non-resectable liver metastases.
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Affiliation(s)
- Jin C Kim
- Department of Surgery, University of Ulsan College of Medicine, 388-1 Poongnap-2-Dong, Songpa-Ku, Seoul 138-736, Korea.
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