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Degiuli M, Ortenzi M, Tomatis M, Puca L, Cianflocca D, Rega D, Maroli A, Elmore U, Pecchini F, Milone M, La Mendola R, Soligo E, Deidda S, Spoletini D, Cassini D, Aprile A, Mineccia M, Nikaj H, Marchegiani F, Maiello F, Bombardini C, Zuolo M, Carlucci M, Ferraro L, Falato A, Biondi A, Persiani R, Marsanich P, Fusario D, Solaini L, Pollesel S, Rizzo G, Coco C, Di Leo A, Cavaliere D, Roviello F, Muratore A, D’Ugo D, Bianco F, Bianchi PP, De Nardi P, Rigamonti M, Anania G, Belluco C, Polastri R, Pucciarelli S, Gentilli S, Ferrero A, Scabini S, Baldazzi G, Carlini M, Restivo A, Testa S, Parini D, De Palma GD, Piccoli M, Rosati R, Spinelli A, Delrio P, Borghi F, Guerrieri M, Reddavid R. Minimally invasive vs. open segmental resection of the splenic flexure for cancer: a nationwide study of the Italian Society of Surgical Oncology-Colorectal Cancer Network (SICO-CNN). Surg Endosc 2023; 37:977-988. [PMID: 36085382 PMCID: PMC9944710 DOI: 10.1007/s00464-022-09547-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Accepted: 08/07/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND Evidence on the efficacy of minimally invasive (MI) segmental resection of splenic flexure cancer (SFC) is not available, mostly due to the rarity of this tumor. This study aimed to determine the survival outcomes of MI and open treatment, and to investigate whether MI is noninferior to open procedure regarding short-term outcomes. METHODS This nationwide retrospective cohort study included all consecutive SFC segmental resections performed in 30 referral centers between 2006 and 2016. The primary endpoint assessing efficacy was the overall survival (OS). The secondary endpoints included cancer-specific mortality (CSM), recurrence rate (RR), short-term clinical outcomes (a composite of Clavien-Dindo > 2 complications and 30-day mortality), and pathological outcomes (a composite of lymph nodes removed ≧12, and proximal and distal free resection margins length ≧ 5 cm). For these composites, a 6% noninferiority margin was chosen based on clinical relevance estimate. RESULTS A total of 606 patients underwent either an open (208, 34.3%) or a MI (398, 65.7%) SFC segmental resection. At univariable analysis, OS and CSM were improved in the MI group (log-rank test p = 0.004 and Gray's tests p = 0.004, respectively), while recurrences were comparable (Gray's tests p = 0.434). Cox multivariable analysis did not support that OS and CSM were better in the MI group (p = 0.109 and p = 0.163, respectively). Successful pathological outcome, observed in 53.2% of open and 58.3% of MI resections, supported noninferiority (difference 5.1%; 1-sided 95%CI - 4.7% to ∞). Successful short-term clinical outcome was documented in 93.3% of Open and 93.0% of MI procedures, and supported noninferiority as well (difference - 0.3%; 1-sided 95%CI - 5.0% to ∞). CONCLUSIONS Among patients with SFC, the minimally invasive approach met the criterion for noninferiority for postoperative complications and pathological outcomes, and was found to provide results of OS, CSM, and RR comparable to those of open resection.
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Affiliation(s)
- Maurizio Degiuli
- University of Turin, Department of Oncology, San Luigi University Hospital, Div of Surgical Oncology, Orbassano, Turin, Italy. .,Department of Oncology, Head Surgical Oncology and Digestive Surgery, University of Torino, San Luigi University Hospital, Regione Gonzole 10 Orbassano, 10043, Turin, Italy.
| | - Monica Ortenzi
- grid.411490.90000 0004 1759 6306Clinica Chirurgica Universita’ Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy
| | - Mariano Tomatis
- grid.7605.40000 0001 2336 6580BSIT, Department of Oncology, University of Turin, Orbassano, Turin, Italy
| | - Lucia Puca
- grid.7605.40000 0001 2336 6580University of Turin, Department of Oncology, San Luigi University Hospital, Div of Surgical Oncology, Orbassano, Turin, Italy
| | - Desiree Cianflocca
- grid.413179.90000 0004 0486 1959Department of Surgery, S. Croce e Carle Hospital, Cuneo, Italy ,grid.432329.d0000 0004 1789 4477Department of General and Emergency Surgery, Azienda Ospedaliero Universitaria, Città della Salute e della Scienza, Turin, Italy
| | - Daniela Rega
- Colorectal Surgical Oncology, Abdominal Oncology Department, Fondazione Giovanni Pascale IRCCS, Naples, Italy
| | - Annalisa Maroli
- grid.417728.f0000 0004 1756 8807Colon and Rectal Surgery Division, Humanitas Clinical and Research Center, Via Alessandro Manzoni, 56, Rozzano, 20089 Milan, Italy
| | - Ugo Elmore
- grid.15496.3f0000 0001 0439 0892Division of Gastrointestinal Surgery, Vita Salute University, San Raffaele Hospital, 20132 Milan, Italy
| | - Francesca Pecchini
- grid.7548.e0000000121697570Unita’ Operativa di chirurgia generale, d’urgenza e nuove tecnologie, OCSAE, Azienda Ospedaliero Universitaria di Modena, Modena, Italy
| | - Marco Milone
- grid.4691.a0000 0001 0790 385XDepartment of Clinical Medicine and Surgery, Department of Gastroenterology, Endocrinology and Endoscopic Surgery, University of Naples “Federico II”, Naples, Italy
| | - Roberta La Mendola
- grid.415200.20000 0004 1760 6068General Surgery Unit, Santa Maria della Misericordia Hospital, Rovigo, Italy
| | - Erica Soligo
- grid.415230.10000 0004 1757 123XS.C. Chirurgia Generale, Ospedale S. Andrea, Vercelli, Italy
| | - Simona Deidda
- grid.7763.50000 0004 1755 3242Chirurgia Coloproctologica-AOU Cagliari, Dipartimento di Scienze Chirurgiche, Università di Cagliari, Cagliari, Italy
| | - Domenico Spoletini
- grid.416628.f0000 0004 1760 4441UOC Chirurgia Generale, Ospedale S. Eugenio, Piazzale dell’Umanesimo, 10, 00144 Rome, Italy
| | - Diletta Cassini
- Unità Operativa Complessa di Chirurgia Generale, P.O. SSG, ASST NORD MILANO, Milan, Italy
| | - Alessandra Aprile
- grid.410345.70000 0004 1756 7871Surgical Oncology Surgery, IRCCS Policlinico San Martino, Genoa, Italy
| | - Michela Mineccia
- grid.414700.60000 0004 0484 5983Department of General and Oncological Surgery, ”Umberto I” Mauriziano Hospital, Turin, Italy
| | - Herald Nikaj
- grid.412824.90000 0004 1756 8161SCDU Clinica Chirurgica, General Surgery Department, AOU “Maggiore Della Carità” Hospital, Novara, Italy
| | - Francesco Marchegiani
- grid.5608.b0000 0004 1757 3470Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Padua, Italy
| | - Fabio Maiello
- Department of Surgery, General Surgery Unit, Hospital of Biella, Biella, Italy
| | - Cristina Bombardini
- Department of Surgical Morphology and Experimental Medicine, AOU Ferrara, Ferrara, Italy
| | - Michele Zuolo
- General Surgery Division, “Valli del Noce” Hospital, Cles, Provincial Agency for Health Services (APSS), Trento, Italy
| | - Michele Carlucci
- grid.18887.3e0000000417581884Gastrointestinal Surgery, San Raffaele Hospital, 20132 Milan, Italy
| | - Luca Ferraro
- grid.4708.b0000 0004 1757 2822Division of General and Robotic Surgery, Dipartimento di Scienze della Salute, Università di Milano, 20142 Milan, Italy
| | - Armando Falato
- General Surgery Unit, San Leonardo Hospital, ASL-NA3sud, Castellammare di Stabbia, Naples, Italy
| | - Alberto Biondi
- grid.414603.4Fondazione Policlinico Gemelli, IRCCS, AREA di Chirurgia Addominale, Rome, Italy
| | - Roberto Persiani
- grid.414603.4Fondazione Policlinico Gemelli, IRCCS, AREA di Chirurgia Addominale, Rome, Italy
| | | | - Daniele Fusario
- grid.9024.f0000 0004 1757 4641UOC General and Oncological Surgery, University of Siena, Siena, Italy
| | - Leonardo Solaini
- grid.415079.e0000 0004 1759 989XGeneral and Oncologic Surgery, Morgagni-Pierantoni Hospital, Ausl Romagna, Forlì, Italy
| | - Sara Pollesel
- grid.414603.4Fondazione Policlinico Universitario A. Gemelli, IRCCS, Chirurgia Generale Presidio Columbus, Rome, Italy
| | - Gianluca Rizzo
- grid.414603.4Fondazione Policlinico Universitario A. Gemelli, IRCCS, Chirurgia Generale Presidio Columbus, Rome, Italy
| | - Claudio Coco
- grid.414603.4Fondazione Policlinico Universitario A. Gemelli, IRCCS, Chirurgia Generale Presidio Columbus, Rome, Italy
| | | | - Davide Cavaliere
- grid.414603.4Department of Surgical Oncology, CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy
| | - Franco Roviello
- grid.414603.4Fondazione Policlinico Universitario A. Gemelli, IRCCS, Chirurgia Generale Presidio Columbus, Rome, Italy
| | - Andrea Muratore
- Surgical Department, Edoardo Agnelli Hospital, Pinerolo, Italy
| | - Domenico D’Ugo
- grid.414603.4Fondazione Policlinico Gemelli, IRCCS, AREA di Chirurgia Addominale, Rome, Italy
| | - Francesco Bianco
- General Surgery Unit, San Leonardo Hospital, ASL-NA3sud, Castellammare di Stabbia, Naples, Italy
| | - Paolo Pietro Bianchi
- grid.4708.b0000 0004 1757 2822Division of General and Robotic Surgery, Dipartimento di Scienze della Salute, Università di Milano, 20142 Milan, Italy ,grid.415928.3Department of Surgery, Misericordia Hospital, Grosseto, Italy
| | - Paola De Nardi
- grid.4708.b0000 0004 1757 2822Division of General and Robotic Surgery, Dipartimento di Scienze della Salute, Università di Milano, 20142 Milan, Italy
| | - Marco Rigamonti
- General Surgery Division, “Valli del Noce” Hospital, Cles, Provincial Agency for Health Services (APSS), Trento, Italy
| | - Gabriele Anania
- Department of Surgical Morphology and Experimental Medicine, AOU Ferrara, Ferrara, Italy
| | - Claudio Belluco
- grid.414603.4Department of Surgical Oncology, CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy
| | - Roberto Polastri
- Department of Surgery, General Surgery Unit, Hospital of Biella, Biella, Italy
| | - Salvatore Pucciarelli
- grid.5608.b0000 0004 1757 3470Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Padua, Italy
| | - Sergio Gentilli
- grid.412824.90000 0004 1756 8161SCDU Clinica Chirurgica, General Surgery Department, AOU “Maggiore Della Carità” Hospital, Novara, Italy
| | - Alessandro Ferrero
- grid.414700.60000 0004 0484 5983Department of General and Oncological Surgery, ”Umberto I” Mauriziano Hospital, Turin, Italy
| | - Stefano Scabini
- grid.410345.70000 0004 1756 7871Surgical Oncology Surgery, IRCCS Policlinico San Martino, Genoa, Italy
| | - Gianandrea Baldazzi
- Unità Operativa Complessa di Chirurgia Generale, P.O. SSG, ASST NORD MILANO, Milan, Italy
| | - Massimo Carlini
- grid.416628.f0000 0004 1760 4441UOC Chirurgia Generale, Ospedale S. Eugenio, Piazzale dell’umanesimo, 10, 00144 Rome, Italy
| | - Angelo Restivo
- grid.7763.50000 0004 1755 3242Chirurgia Coloproctologica-AOU Cagliari, Dipartimento di Scienze Chirurgiche, Università di Cagliari, Cagliari, Italy
| | - Silvio Testa
- grid.415230.10000 0004 1757 123XS.C. Chirurgia Generale, Ospedale S. Andrea, Vercelli, Italy
| | - Dario Parini
- grid.415200.20000 0004 1760 6068General Surgery Unit, Santa Maria della Misericordia Hospital, Rovigo, Italy
| | - Giovanni Domenico De Palma
- grid.4691.a0000 0001 0790 385XDepartment of Clinical Medicine and Surgery, Department of Gastroenterology, Endocrinology and Endoscopic Surgery, University of Naples “Federico II”, Naples, Italy
| | - Micaela Piccoli
- grid.7548.e0000000121697570Unita’ Operativa di chirurgia generale, d’urgenza e nuove tecnologie, OCSAE, Azienda Ospedaliero Universitaria di Modena, Modena, Italy
| | - Riccardo Rosati
- grid.15496.3f0000 0001 0439 0892Division of Gastrointestinal Surgery, Vita Salute University, San Raffaele Hospital, 20132 Milan, Italy
| | - Antonino Spinelli
- grid.417728.f0000 0004 1756 8807Humanitas Clinical and Research Center, Via Alessandro Manzoni, 56 Rozzano, 20089 Milan, Italy ,grid.452490.eDepartment of Biomedical Science, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Paolo Delrio
- Colorectal Surgical Oncology, Abdominal Oncology Department, Fondazione Giovanni Pascale IRCCS, Naples, Italy
| | - Felice Borghi
- grid.413179.90000 0004 0486 1959Department of Surgery, S. Croce e Carle Hospital, Cuneo, Italy ,grid.419555.90000 0004 1759 7675Oncological Surgery, Candiolo Cancer Institute-FPO-IRCCS, Candiolo, 10060 Torino, Italy
| | - Marco Guerrieri
- grid.411490.90000 0004 1759 6306Clinica Chirurgica Universita’ Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy
| | - Rossella Reddavid
- grid.7605.40000 0001 2336 6580University of Turin, Department of Oncology, San Luigi University Hospital, Div of Surgical Oncology, Orbassano, Turin, Italy
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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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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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Huang BS, Horng HC, Wang PH, Yang MH, Chen YJ. Response to comment on "Oestrogen-induced angiogenesis and implantation contribute to the development of parasitic myomas after laparoscopic morcellation". Reprod Biol Endocrinol 2017; 15:55. [PMID: 28732509 PMCID: PMC5521145 DOI: 10.1186/s12958-017-0270-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Accepted: 06/17/2017] [Indexed: 11/10/2022] Open
Abstract
According to the literature review, CO2 insufflation on parasitic myoma implantation is not well studied, and we concur that our study is related to "Morcellation-induced parasitic myomas." We did not compare CO2 insufflation to non-insufflation in our study. The reason is the efficacy of gasless laparoscopic myomectomy and morcellation is not well established and this modality is seldom performed. Moreover, the effects of pneumoperitoneum on mesothelial cells and the role of the entire peritoneal cavity as a cofactor in adhesion formation have become well established, the role of CO2 insufflation in the establishment of parasitic myomas has not yet been studied. As such, more in-depth and well-designed studies for the role of CO2 insufflation are needed.
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Affiliation(s)
- Ben-Shian Huang
- 0000 0004 0604 5314grid.278247.cDepartment of Obstetrics and Gynaecology, Taipei Veterans General Hospital, No.201, Sec. 2, Shih-Pai Road, Taipei, 112 Taiwan
- 0000 0004 1767 1097grid.470147.1Department of Obstetrics and Gynaecology, National Yang-Ming University Hospital, No.152, Xin-Min Road, Yilan, 260 Taiwan
- Department of Obstetrics and Gynaecology, School of Medicine, No.155, Sec.2, Li-Nong Street, Taipei, 112 Taiwan
- 0000 0001 0425 5914grid.260770.4Institute of Clinical Medicine, National Yang-Ming University, No.155, Sec.2, Li-Nong Street, Taipei, 112 Taiwan
| | - Huann-Cheng Horng
- 0000 0004 0604 5314grid.278247.cDepartment of Obstetrics and Gynaecology, Taipei Veterans General Hospital, No.201, Sec. 2, Shih-Pai Road, Taipei, 112 Taiwan
- Department of Obstetrics and Gynaecology, School of Medicine, No.155, Sec.2, Li-Nong Street, Taipei, 112 Taiwan
| | - Peng-Hui Wang
- 0000 0004 0604 5314grid.278247.cDepartment of Obstetrics and Gynaecology, Taipei Veterans General Hospital, No.201, Sec. 2, Shih-Pai Road, Taipei, 112 Taiwan
- Department of Obstetrics and Gynaecology, School of Medicine, No.155, Sec.2, Li-Nong Street, Taipei, 112 Taiwan
- 0000 0001 0425 5914grid.260770.4Institute of Clinical Medicine, National Yang-Ming University, No.155, Sec.2, Li-Nong Street, Taipei, 112 Taiwan
| | - Muh-Hwa Yang
- 0000 0001 0425 5914grid.260770.4Institute of Clinical Medicine, National Yang-Ming University, No.155, Sec.2, Li-Nong Street, Taipei, 112 Taiwan
| | - Yi-Jen Chen
- 0000 0004 0604 5314grid.278247.cDepartment of Obstetrics and Gynaecology, Taipei Veterans General Hospital, No.201, Sec. 2, Shih-Pai Road, Taipei, 112 Taiwan
- Department of Obstetrics and Gynaecology, School of Medicine, No.155, Sec.2, Li-Nong Street, Taipei, 112 Taiwan
- 0000 0001 0425 5914grid.260770.4Institute of Clinical Medicine, National Yang-Ming University, No.155, Sec.2, Li-Nong Street, Taipei, 112 Taiwan
- 0000 0004 0572 7890grid.413846.cDepartment of Obstetrics and Gynaecology, Cheng-Hsin General Hospital, No.45, Cheng Hsin St., Pei-Tou, Taipei Taiwan
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Huang BS, Yang MH, Wang PH, Li HY, Chou TY, Chen YJ. Oestrogen-induced angiogenesis and implantation contribute to the development of parasitic myomas after laparoscopic morcellation. Reprod Biol Endocrinol 2016; 14:64. [PMID: 27716434 PMCID: PMC5053344 DOI: 10.1186/s12958-016-0200-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Accepted: 09/29/2016] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Iatrogenic parasitic myomas (PMs), caused by intra-corporeal power morcellation during laparoscopy is gradually increasing. However, the pathogenesis and medical treatment of PMs remain largely unelucidated. METHODS Laparoscopically-induced PM xenografted mouse model was conducted by xenografting human uterine myoma fragments into the abdominal cavity of SCID mice and hormonal manipulation was performed using this mouse model to demonstrate the role of oestrogen in the development of implanted PMs. Immunohistochemistry of oestrogen receptor α (ERα), progesterone receptor (PR), vimentin, vascular endothelial growth factor (VEGF), microvessel density (MVD) and Ki-67 index was performed and compared. RESULTS In the patient with PMs, ERα, PR, angiogenesis and proliferative property expression were upregulated in PM lesions compared to uterine myomas. In the laparoscopically-induced PM mouse model, implanted myomas had more steroid receptor expressions, angiogenesis and proliferative property compared with pre-xenografted or non-implanted myoma. Depletion of oestrogen in the ovariectomized (OVX) mice decreased laparoscopically-induced PM implantations. In comparison, the implantations of PMs were increased with additional E2 supplement. Hormonal manipulation in the PM mouse model, including AI, GnRHa and SERM groups, were compared and AI significantly decreased the implantations, steroid receptor, angiogenesis, cell density, and proliferative index of PMs compared with control group. Furthermore, GnRHa significantly decreased VEGF and MVD expressions compared with control group. CONCLUSIONS These data highlight the crucial role of oestrogen in the development of laparoscopically-induced PMs and suggest that hormone manipulation may be a potential therapeutic agent. TRIAL REGISTRATION This protocol was approved by the Human and Animal Institutional Review Board of Taipei Veterans General Hospital ( VGHIRB No 2014-10-002C on Nov. 17th, 2014; IACUC 2014-119 on Aug. 22nd, 2014).
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Affiliation(s)
- Ben-Shian Huang
- Department of Obstetrics and Gynaecology, Taipei Veterans General Hospital, No.201, Sec. 2, Shih-Pai Road, Taipei, 112 Taiwan
- Department of Obstetrics and Gynaecology, National Yang-Ming University Hospital, No.169, Siaoshe Road, Yilan, 260 Taiwan
- Department of Obstetrics and Gynaecology, School of Medicine, National Yang-Ming University, No.155, Sec.2, Li-Nong Street, Taipei, 112 Taiwan
- Institute of Clinical Medicine, National Yang-Ming University, No.155, Sec.2, Li-Nong Street, Taipei, 112 Taiwan
| | - Muh-Hwa Yang
- Institute of Clinical Medicine, National Yang-Ming University, No.155, Sec.2, Li-Nong Street, Taipei, 112 Taiwan
| | - Peng-Hui Wang
- Department of Obstetrics and Gynaecology, Taipei Veterans General Hospital, No.201, Sec. 2, Shih-Pai Road, Taipei, 112 Taiwan
- Department of Obstetrics and Gynaecology, School of Medicine, National Yang-Ming University, No.155, Sec.2, Li-Nong Street, Taipei, 112 Taiwan
- Institute of Clinical Medicine, National Yang-Ming University, No.155, Sec.2, Li-Nong Street, Taipei, 112 Taiwan
| | - Hsin-Yang Li
- Department of Obstetrics and Gynaecology, Taipei Veterans General Hospital, No.201, Sec. 2, Shih-Pai Road, Taipei, 112 Taiwan
| | - Teh-Ying Chou
- Institute of Clinical Medicine, National Yang-Ming University, No.155, Sec.2, Li-Nong Street, Taipei, 112 Taiwan
| | - Yi-Jen Chen
- Department of Obstetrics and Gynaecology, Taipei Veterans General Hospital, No.201, Sec. 2, Shih-Pai Road, Taipei, 112 Taiwan
- Department of Obstetrics and Gynaecology, School of Medicine, National Yang-Ming University, No.155, Sec.2, Li-Nong Street, Taipei, 112 Taiwan
- Institute of Clinical Medicine, National Yang-Ming University, No.155, Sec.2, Li-Nong Street, Taipei, 112 Taiwan
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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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8
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Schroeder M, Viezens L, Wellbrock J, Fiedler W, Rüther W, Algenstaedt P, Hansen-Algenstaedt N, Schaefer C. Sunitinib treatment reduces tumor growth and limits changes in microvascular properties after minor surgical intervention in an in vivo model of secondary breast cancer growth in bone. J Surg Oncol 2016; 113:515-21. [DOI: 10.1002/jso.24185] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Accepted: 01/13/2016] [Indexed: 01/10/2023]
Affiliation(s)
- Malte Schroeder
- Department of Trauma, Hand, and Reconstructive Surgery; University Medical Center Hamburg-Eppendorf; Hamburg Germany
- Department of Orthopaedics; University Medical Center Hamburg-Eppendorf; Hamburg Germany
| | - Lennart Viezens
- Department of Trauma, Hand, and Reconstructive Surgery; University Medical Center Hamburg-Eppendorf; Hamburg Germany
- Department of Orthopaedics; University Medical Center Hamburg-Eppendorf; Hamburg Germany
| | - Jasmin Wellbrock
- Department of Oncology and Hematology With The Sections Pneumonology and Bone Marrow Transplantation; Hubertus Wald Tumor Center; University Cancer Center Hamburg; University Medical Center Hamburg-Eppendorf; Hamburg Germany
| | - Walter Fiedler
- Department of Oncology and Hematology With The Sections Pneumonology and Bone Marrow Transplantation; Hubertus Wald Tumor Center; University Cancer Center Hamburg; University Medical Center Hamburg-Eppendorf; Hamburg Germany
| | - Wolfgang Rüther
- Department of Orthopaedics; University Medical Center Hamburg-Eppendorf; Hamburg Germany
| | - Petra Algenstaedt
- Department of Internal Medicine; University Medical Center Hamburg-Eppendorf; Germany
- Medicum Eppendorf; Hamburg Germany
| | - Nils Hansen-Algenstaedt
- Department of Orthopaedics; University Medical Center Hamburg-Eppendorf; Hamburg Germany
- OrthoCentrum Hamburg; Parkklinik Manhagen; Hamburg Germany
| | - Christian Schaefer
- Department of Orthopaedics; University Medical Center Hamburg-Eppendorf; Hamburg Germany
- Department of Spine Surgery; Klinikum Bad Bramstedt; Bad Bramstedt Germany
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9
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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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10
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Matsuzaki S, Canis M, Botchorishvili R. "Gain more working space at a low intraperitoneal pressure" may be a difficult, but worthy anesthesiologic challenge. REVISTA ESPANOLA DE ANESTESIOLOGIA Y REANIMACION 2014; 61:2-5. [PMID: 24342168 DOI: 10.1016/j.redar.2013.10.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/17/2013] [Accepted: 10/21/2013] [Indexed: 06/03/2023]
Affiliation(s)
- S Matsuzaki
- CHU Clermont-Ferrand, CHU Estaing, Chirurgie Gynécologique, Clermont-Ferrand, France; Clermont Université, Université d'Auvergne, ISIT UMR6284, Clermont-Ferrand, France; CNRS, ISIT UMR6284, Clermont-Ferrand, France.
| | - M Canis
- CHU Clermont-Ferrand, CHU Estaing, Chirurgie Gynécologique, Clermont-Ferrand, France; Clermont Université, Université d'Auvergne, ISIT UMR6284, Clermont-Ferrand, France; CNRS, ISIT UMR6284, Clermont-Ferrand, France
| | - R Botchorishvili
- CHU Clermont-Ferrand, CHU Estaing, Chirurgie Gynécologique, Clermont-Ferrand, France; Clermont Université, Université d'Auvergne, ISIT UMR6284, Clermont-Ferrand, France; CNRS, ISIT UMR6284, Clermont-Ferrand, France
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11
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Huang SG, Li YP, Zhang Q, Redmond HP, Wang JH, Wang J. Laparotomy and laparoscopy diversely affect macrophage-associated antimicrobial activity in a murine model. BMC Immunol 2013; 14:27. [PMID: 23786397 PMCID: PMC3711975 DOI: 10.1186/1471-2172-14-27] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2013] [Accepted: 06/18/2013] [Indexed: 02/08/2023] Open
Abstract
Background Surgical intervention-related trauma contributes largely to the development of postoperative immunosuppression, with reduced resistance to secondary bacterial infection. This study compared the impact of laparotomy versus laparoscopy on macrophage-associated bactericidal ability and examined whether laparotomy renders the host more susceptible to microbial infection. Results BALB/c mice were randomized into control, laparotomy, and laparoscopy groups. Laparotomy, but not laparoscopy, significantly downregulated CR3 expression on macrophages, diminished macrophage-induced uptake and phagocytosis of E. coli and S. aureus, and impaired macrophage-mediated intracellular bacterial killing. Consistent with this, mice that underwent laparotomy displayed substantially higher bacterial counts in the blood and visceral organs as well as a significantly enhanced mortality rate following bacterial infection, whereas mice subjected to laparoscopy did not show any defects in their bacterial clearance. Conclusion Laparotomy has an adverse effect on host innate immunity against microbial infection by impairing macrophage-mediated phagocytosis and killing of the invaded bacteria. By contrast, laparoscopy appears to preserve macrophage-associated bactericidal ability, thus alleviating the development of postoperative immunosuppression.
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Affiliation(s)
- Shun Gen Huang
- Department of Pediatric Surgery, Affiliated Children's Hospital, Soochow University, Suzhou, China
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12
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Kim YW, Kim IY. The Role of Surgery for Asymptomatic Primary Tumors in Unresectable Stage IV Colorectal Cancer. Ann Coloproctol 2013; 29:44-54. [PMID: 23700570 PMCID: PMC3659242 DOI: 10.3393/ac.2013.29.2.44] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2013] [Accepted: 04/01/2013] [Indexed: 02/08/2023] Open
Abstract
There are still debates regarding the appropriate primary treatment policy for asymptomatic primary colorectal lesions in cases of unresectable metastatic colorectal cancer. Even though there are patients with asymptomatic primary tumors when starting chemotherapy, those patients may still undergo surgery due to complications related to primary tumors in the middle of chemotherapy; therefore, controversy exists regarding surgical resection of primary colorectal lesions in cases where symptoms are absent when making a diagnosis. Thus, based on the published literature, we discuss opinions that prefer first-line surgery for primary tumors as well as opinions favoring first-line chemotherapy for treating unresectable synchronous metastatic colorectal cancer. Although the upfront chemotherapy including targeted agents is suggested as an effective treatment in recent years, the first line surgery has been a preferred treatment for decades. The first line surgery is beneficial to prolong the survival duration given the retrospective analysis of randomized trial data. So far, no prospective comparison study has only focused on the first-line treatment modality; thus, future clinical studies focusing on the survival duration and the quality of life should be performed as soon as possible. Furthermore, at this point, multidisciplinary team approaches would be helpful in finding the appropriate therapy. Regardless of symptoms, the performance status and the tumor burden should be taken into consideration as well. In case of surgical resection, minimally invasive surgery, such as laparoscopic surgery, is recommended.
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Affiliation(s)
- Young Wan Kim
- Department of Surgery, Yonsei University Wonju College of Medicine, Wonju, Korea
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13
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Kim YW, Kim IY. The Role of Surgery for Asymptomatic Primary Tumors in Unresectable Stage IV Colorectal Cancer. Ann Coloproctol 2013. [PMID: 23700570 DOI: 10.3393/ac.2013.3329.3392.3344] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
There are still debates regarding the appropriate primary treatment policy for asymptomatic primary colorectal lesions in cases of unresectable metastatic colorectal cancer. Even though there are patients with asymptomatic primary tumors when starting chemotherapy, those patients may still undergo surgery due to complications related to primary tumors in the middle of chemotherapy; therefore, controversy exists regarding surgical resection of primary colorectal lesions in cases where symptoms are absent when making a diagnosis. Thus, based on the published literature, we discuss opinions that prefer first-line surgery for primary tumors as well as opinions favoring first-line chemotherapy for treating unresectable synchronous metastatic colorectal cancer. Although the upfront chemotherapy including targeted agents is suggested as an effective treatment in recent years, the first line surgery has been a preferred treatment for decades. The first line surgery is beneficial to prolong the survival duration given the retrospective analysis of randomized trial data. So far, no prospective comparison study has only focused on the first-line treatment modality; thus, future clinical studies focusing on the survival duration and the quality of life should be performed as soon as possible. Furthermore, at this point, multidisciplinary team approaches would be helpful in finding the appropriate therapy. Regardless of symptoms, the performance status and the tumor burden should be taken into consideration as well. In case of surgical resection, minimally invasive surgery, such as laparoscopic surgery, is recommended.
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Affiliation(s)
- Young Wan Kim
- Department of Surgery, Yonsei University Wonju College of Medicine, Wonju, Korea
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14
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Zerey M, Hawver LM, Awad Z, Stefanidis D, Richardson W, Fanelli RD. SAGES evidence-based guidelines for the laparoscopic resection of curable colon and rectal cancer. Surg Endosc 2013; 27:1-10. [PMID: 23239291 DOI: 10.1007/s00464-012-2592-x] [Citation(s) in RCA: 77] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2012] [Accepted: 06/11/2012] [Indexed: 02/07/2023]
Affiliation(s)
- Marc Zerey
- Department of Surgery, Sansum Clinic, Santa Barbara, CA, USA.
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15
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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: 52] [Impact Index Per Article: 4.0] [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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16
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Laparoscopic Surgery for Benign and Malignant Colorectal Diseases. Surg Laparosc Endosc Percutan Tech 2012; 22:165-74. [DOI: 10.1097/sle.0b013e31824be7ba] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Abstract
Laparoscopy has emerged as a useful tool in the surgical treatment of diseases of the colon and rectum. Specifically, in the application of colon cancer, a laparoscopic-assisted approach offers short-term benefits to patients while maintaining a long-term oncologic outcome. Hand-assisted laparoscopic surgery may help decrease operative times while preserving the benefits of laparoscopy. The literature on the use of laparoscopy for rectal cancer is still in its early stages. Limited data suggest short-term benefits without compromising oncologic outcome; however, data from large multicenter trials will clarify the role of laparoscopy in the treatment of rectal cancer. Robotic proctectomy is a novel technique that may offer considerable advantage and overcome some limitations laparoscopy creates while working in the confines of the pelvis. The improved magnification and visualization offered with the robot may also assist in preserving bladder and sexual function. Transanal endoscopic microsurgery (TEM) for the treatment of T1 rectal cancers with low-risk features appears to be safe. However, TEM has a significantly higher recurrence rate when used to treat invasive cancer. Endoluminal techniques and equipment are under development and could offer more minimally invasive approaches to the treatment of colon and rectal cancer. Credentialing and training of surgeons and teams involved in the use of laparoscopy is important prior to making these techniques ubiquitous.
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Affiliation(s)
- Govind Nandakumar
- Section of Colon and Rectal Surgery, Washington University School of Medicine, St. Louis, Missouri
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18
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Schaefer C, Fuhrhop I, Schroeder M, Viezens L, Otten J, Fiedler W, Rüther W, Hansen-Algenstaedt N. Microcirculation of secondary bone tumors in vivo: the impact of minor surgery at a distal site. J Orthop Res 2010; 28:1515-21. [PMID: 20872590 DOI: 10.1002/jor.21166] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Microcirculatory properties of tumors play a pivotal role in tumor progression and inefficacy of therapies. It has been hypothesized that surgical interventions result in an accelerated tumor growth by increasing the level of pro-angiogenic cytokines with subsequent amplification of tumor angiogenesis. To characterize the microvascular properties of secondary bone tumors in vivo and determine the impact of minor surgery on the microcirculation, we performed intravital microscopy over 25 days using a xenograft model of breast cancer tumor growth (MCF-7) in bone. After engraftment of tumors the mice were treated with a mastectomy versus no surgery. Tumor growth was accompanied by angiogenic sprouting and decreased vascular diameters while blood flow rate and tumor perfusion remained constant. Mastectomy initially led to a significant reduction of functional vascular density, increased vascular diameter, and decreased blood flow velocities. However, neither tumor growth nor tissue perfusion was different between the groups. The presented study corroborates the assumption that tumor microcirculation in bone exhibits similar time-dependent alterations compared to soft tissue tumors. A minor surgical intervention did not change tumor growth kinetics however microcirculatory properties were altered. Whether major surgery has an impact on tumor growth in bone should be clarified in further studies.
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Affiliation(s)
- Christian Schaefer
- Orthopaedic Spine Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
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19
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Minimally invasive colorectal resection for cancer is associated with a short-lived decrease in soluble Tie-2 receptor levels, which may transiently inhibit VEGF-mediated angiogenesis (via altered blood levels of free Ang-1 and Ang-2). Surg Endosc 2010; 24:2581-7. [DOI: 10.1007/s00464-010-1008-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2009] [Accepted: 02/15/2010] [Indexed: 12/22/2022]
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20
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Minimally invasive colorectal resection is associated with a rapid and sustained decrease in plasma levels of epidermal growth factor (EGF) in the colon cancer setting. Surg Endosc 2010; 24:2617-22. [PMID: 20354877 DOI: 10.1007/s00464-010-1018-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2009] [Accepted: 03/07/2010] [Indexed: 02/08/2023]
Abstract
BACKGROUND Epidermal growth factor (EGF) stimulates tumor growth directly via tumor cell EGF receptors or indirectly via its proangiogenic effects. This study's purpose was to determine the impact of minimally invasive colorectal resection (MICR) on postoperative (postop) plasma EGF levels in the colorectal cancer (CRC) and benign disease settings and to see if preoperative (PreOp) EGF levels are altered in cancer patients. METHODS MICR patients with benign pathology (n = 40) and CRC (n = 48) had blood samples taken PreOp and on postoperative days (POD) 1 and 3. In some patients, late samples were taken between POD7 and POD60; these were bundled into 7-day blocks and considered as single time points. EGF levels were determined by enzyme-linked immunosorbent assay (ELISA) and results were reported as mean ± SD after logarithmic transformation. The Student t test was used (p < 0.008 after Bonferroni correction). RESULTS The cancer and benign groups were comparable except for age. The mean PreOp CRC plasma EGF level (122.9 ± 75.9 pg/ml) was significantly higher than that of the benign group (85.3 ± 38.5 pg/ml) (p = 0.015). The cancer group's EGF levels were significantly decreased on POD1 and POD3 and for the POD31-55 time point (mean EGF level = 63.1 ± 42.2 (n = 10). The benign group's POD3 and POD7-14 EGF levels were significantly lower than the PreOp level; later levels returned toward baseline. Small late sample size limited analysis. CONCLUSION Plasma EGF levels are significantly higher in cancer patients. MICR is associated with a significant decrease in EGF levels early postop in both cancer and benign settings. Unlike the benign group, EGF blood levels in cancer patients remain low during the second postop month. A larger study with more late samples is needed to verify these results. EGF may have value as a tumor marker.
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21
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Shantha Kumara HMC, Cabot JC, Hoffman A, Luchtefeld M, Kalady MF, Hyman N, Feingold D, Baxter R, Whelan RL. Minimally invasive colon resection for malignant colonic conditions is associated with a transient early increase in plasma sVEGFR1 and a decrease in sVEGFR2 levels after surgery. Surg Endosc 2009; 24:283-9. [DOI: 10.1007/s00464-009-0575-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2009] [Accepted: 05/14/2009] [Indexed: 10/20/2022]
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22
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Ceelen WP, Bracke ME. Peritoneal minimal residual disease in colorectal cancer: mechanisms, prevention, and treatment. Lancet Oncol 2009; 10:72-9. [PMID: 19111247 DOI: 10.1016/s1470-2045(08)70335-8] [Citation(s) in RCA: 89] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Roughly one in five patients with colorectal cancer develops peritoneal minimal residual disease after surgical resection, and about one in seven patients develops peritoneal carcinomatosis. By contrast with the vast body of research addressing haematogenous metastasis, little is known about the biology of peritoneal spread of colorectal cancer. The development of peritoneal carcinomatosis involves well-defined steps including cell shedding and transport, adhesion to the mesothelial layer, invasion of and proliferation into the submesothelial stroma, and potential access to the systemic circulation. In this Review, we summarise the molecular mechanisms and potential preventive measures associated with each step of the peritoneal metastatic cascade.
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Affiliation(s)
- Wim P Ceelen
- Department of Surgical Oncology, Ghent University Hospital, Ghent, Belgium
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23
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Soop M, Nelson H. Is laparoscopic resection appropriate for colorectal adenocarcinoma? Adv Surg 2008; 42:205-17. [PMID: 18953819 DOI: 10.1016/j.yasu.2008.03.010] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Oncologic safety has now been demonstrated for laparoscopy-assisted surgery for colon adenocarcinoma after 3 and 5 years of follow-up. Pooled data from large multicenter and smaller single-center trials demonstrate that the modality conveys significant short-term benefits as compared with open surgery, although the full potential has probably not yet been reached. Currently, the data supports improvements in wound morbidity, intraoperative blood loss, narcotic analgesia requirements, time to resumption of bowel movements, and time to discharge from hospital. There is a large potential for improved short-term results when combined with current and developing enhanced-recovery programs. For rectal cancer, the role of laparoscopic surgery is less clear. Data from the first large multicenter trial suggest that laparoscopic dissection may compromise the circumferential resection margin, and this issue will be the focus of ongoing and planned trials. Certain short-term benefits have been shown in pooled analyses of smaller nonrandomized trials, such as a decrease in overall morbidity and a marked reduction of duration of postoperative hospital stay.
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Affiliation(s)
- Mattias Soop
- Division of Colon and Rectal Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
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24
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The long-term results of a randomized clinical trial of laparoscopy-assisted versus open surgery for colon cancer. Ann Surg 2008; 248:1-7. [PMID: 18580199 DOI: 10.1097/sla.0b013e31816a9d65] [Citation(s) in RCA: 431] [Impact Index Per Article: 25.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE The aim of this study was to compare the long-term outcome of laparoscopy-assisted colectomy (LAC) and open colectomy (OC) for nonmetastatic colon cancer. METHODS From November 1993 to July 1998 all patients with adenocarcinoma of the colon were assessed for entry in this single center, clinically randomized trial. Adjuvant therapy and postoperative follow-up were similar in both groups. The primary endpoint was cancer-related survival and secondary endpoints were probability of overall survival and probability of being free of recurrence. Data were analyzed according the intention-to-treat principle. RESULTS Two hundred and nineteen patients entered the study (111 LAC group and 108 OC group). The median follow-up was 95 months (range, 77-133). There was a tendency of higher cancer-related survival (P = 0.07, NS) and overall survival (P = 0.06, NS) for the LAC group. Probability of cancer-related survival was higher in the LAC group (P = 0.02) when compared with OC. The regression analysis showed that LAC was independently associated with a reduced risk of tumor relapse (hazard ratio 0.47, 95% CI 0.23-0.94), death from a cancer-related cause (0.44, 0.21-0.92) and death from any cause (0.59, 0.35-0.98). CONCLUSIONS LAC is more effective than OC in the treatment of colon cancer.
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25
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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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Steele SR, Brown TA, Rush RM, Martin MJ. Laparoscopic vs open colectomy for colon cancer: results from a large nationwide population-based analysis. J Gastrointest Surg 2008; 12:583-91. [PMID: 17846852 DOI: 10.1007/s11605-007-0286-9] [Citation(s) in RCA: 95] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2007] [Accepted: 07/29/2007] [Indexed: 01/31/2023]
Abstract
PURPOSE Laparoscopic colectomy has only recently become an accepted technique for the treatment of colon cancer. We sought to analyze factors that affect the type of resection performed and associated outcomes from a large nationwide database. METHODS All admissions with a primary diagnosis of colon cancer undergoing elective resection were selected from the 2003 and 2004 Nationwide Inpatient Samples. Multiple linear and logistic regression analyses were used to compare outcome measures and identify independent predictors of a laparoscopic approach. RESULTS We identified 98,923 admissions (mean age 69.2 years). They were predominately Caucasian (81%), had localized disease (63%), had private insurance (56%), and had surgery performed in urban hospitals (87%). Laparoscopic resection was performed in 3,296 cases (3.3%) and was associated with a lower complication rate (18% vs 22%), shorter length of stay (6 vs 7.6 days), decreased need for skilled aftercare (5% vs 11%), and lower mortality (0.6% vs 1.4%, all P<0.01). There was no significant difference in the total hospital charges between the groups ($34,685 vs $34,178, P=0.19). Independent predictors of undergoing laparoscopic resection were age<70 (odds ratio [OR]=1.2, P<0.01), national region (Midwest OR=1.9, West OR=2.0, P<0.01), and lower disease stage (OR=2.5, P<0.01). Ethnic category and insurance status showed no significant association with operative method (P>0.05). CONCLUSIONS Laparoscopy for colon cancer is associated with improved outcomes in unadjusted analysis and similar charges compared to open resection. We found no influence of race or payer status on the utilization of a laparoscopic approach.
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Affiliation(s)
- Scott R Steele
- Department of Surgery, Madigan Army Medical Center, Fort Lewis, WA, USA.
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Feingold DL. Plasma Protein Alterations Associated with Surgery. SEMINARS IN COLON AND RECTAL SURGERY 2007. [DOI: 10.1053/j.scrs.2007.10.006] [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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Demmy TL, Dunn KB. Surgical and Nonsurgical Therapy for Lung Metastasis: Indications and Outcomes. Surg Oncol Clin N Am 2007; 16:579-605, ix. [PMID: 17606195 DOI: 10.1016/j.soc.2007.04.011] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The management of pulmonary metastasis is a broad and multifaceted topic. Because of the filtration function and the favorable microenvironment of the lung, most malignancies cause pulmonary metastases. This article focuses on recent experience with secondary lung malignancies and their newer treatment options, indications, and technical aspects.
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Affiliation(s)
- Todd L Demmy
- Department of Thoracic Surgery, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14231, USA.
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Young-Fadok TM, Fanelli RD, Price RR, Earle DB. Laparoscopic resection of curable colon and rectal cancer: an evidence-based review. Surg Endosc 2007; 21:1063-8. [PMID: 17484010 DOI: 10.1007/s00464-006-9172-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2006] [Accepted: 10/16/2006] [Indexed: 01/20/2023]
Abstract
The initial enthusiastic application of laparoscopic techniques to colorectal surgical procedures was tempered in the early 1990s by reports of tumor implants in the laparoscopic incisions. Substantial evidence has accumulated, including evidence from randomized controlled trials, to support that laparoscopic resection results in oncologic outcomes similar to open resection, when performed by well-trained, experienced surgeons. This review was developed in conjunction with guidelines published by the Society of American Gastrointestinal and Endoscopic Surgeons. Data from the surgical literature concerning laparoscopic resection of curable colorectal cancer was evaluated regarding diagnostic evaluation, preoperative preparation, operative techniques, prevention of tumor implants, and training and experience. Recommendations are accompanied by an assessment of the level of supporting evidence available at the time of the development of the guidelines.
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Affiliation(s)
- T M Young-Fadok
- Division of Colon and Rectal Surgery, Mayo Clinic, Scottsdale, Arizona, United States.
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Bourdel N, Matsuzaki S, Bazin JE, Pouly JL, Mage G, Canis M. Peritoneal tissue-oxygen tension during a carbon dioxide pneumoperitoneum in a mouse laparoscopic model with controlled respiratory support. Hum Reprod 2007; 22:1149-55. [PMID: 17208946 DOI: 10.1093/humrep/del482] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Previous animal studies suggested that the peritoneal environment during a carbon dioxide (CO(2)) pneumoperitoneum is hypoxic and that this may contribute to the formation of intra-abdominal adhesions or the growth of malignant cells. There is no study, however, that investigates the relationship between anaesthesia, ventilation and the laparoscopic peritoneal environment to the development of hypoxia. The objective of this study is to monitor the peritoneal tissue-oxygen tension (PitO(2)) under various conditions including anaesthesia alone, during a CO(2) pneumoperitoneum at both low and high intraperitoneal pressure (IPP), and laparotomy, in animal models with controlled respiratory support (CRS). METHODS C57BL6 mice were divided into eight groups (n = 5) consisting of anaesthesia alone or with CO(2) pneumoperitoneum at low (2 mmHg) or high (8 mmHg) IPP or undergoing laparotomy. Groups were further subdivided into those with or without CRS with endotracheal intubation and mechanical ventilation. Over the course of the 1 h procedure, PitO(2) was continuously monitored. RESULTS Protocol 1. The PitO(2) levels (104.2 +/- 7.8 mmHg, mean +/- SEM) in non-injured peritoneum during a CO(2) pneumoperitoneum at a low IPP were elevated approximately 2-fold over the levels during laparotomy (49.8 +/- 15.0 mmHg) in ventilated mice. Protocol 2. After insufflation with CO(2), the PitO(2) was immediately elevated and maintained at a higher level. Following laparotomy, it decreased immediately. This elevation was not seen with air insufflation. CONCLUSION In mice, a significant elevation in PitO(2) occurs during a CO(2) pneumoperitoneum at low IPP with CRS.
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Affiliation(s)
- Nicolas Bourdel
- Université d'Auvergne - Clermont I, Centre d'Endoscopie et des Nouvelles Techniques Interventionnelles (CENIT), Faculté de Médecine, Clermont-Ferrand, France
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Whitson BA, D'Cunha J, Maddaus MA. Minimally invasive cancer surgery improves patient survival rates through less perioperative immunosuppression. Med Hypotheses 2006; 68:1328-32. [PMID: 17141421 DOI: 10.1016/j.mehy.2006.09.063] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2006] [Accepted: 09/18/2006] [Indexed: 11/19/2022]
Abstract
The import of the immune system to cancer survival is paramount. Immune effector cells are intimately involved in the patient's response to cancer. People with decreased immune function develop cancer more frequently. In the early stages of solid organ malignancies, surgery can potentially be curative. Surgical intervention, in and of itself, is immunosuppressive. Surgical resections are traditionally performed through large incisions. Technologic advances have allowed minimally invasive surgery (MIS) to evolve to the point it is now being used for cancer treatment. Recent minimally invasive series have reported improved survival and recurrence rates, as compared with historical data. We hypothesized that outcome differences for cancer patients undergoing open surgery vs. MIS are due to differential inhibition of immune effector cell function, in response to the different surgical stimulus. This increased immunosuppression after open surgery could potentially inhibit immune effector cell tumor surveillance as well as inhibit scavenging of any residual or micrometastatic disease or of tumor cells shed at the time of the operation. The less immunosuppressive MIS may leave immune function above a threshold level where remaining tumor is cleared. This difference would lead to less recurrence and to survival advantages. A deeper understanding of the integral components of the immune response to surgery would open the door for immunomodulation strategies and be of great clinical utility in guiding neoadjuvant, surgical, or adjuvant therapeutic decisions.
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Affiliation(s)
- B A Whitson
- Section of Thoracic and Foregut Surgery, University of Minnesota, Department of Surgery, MMC 207, 420 Delaware St. SE, Minneapolis, MN 55455, USA.
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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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Ng CSH, Whelan RL, Lacy AM, Yim APC. Is minimal access surgery for cancer associated with immunologic benefits? World J Surg 2005; 29:975-81. [PMID: 15981046 DOI: 10.1007/s00268-005-0029-6] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Minimal-access surgical techniques have been shown to be beneficial to patients in terms of shorter convalescence, reduced pain, and improved cosmesis. Although systemic immune function is better preserved following laparoscopic procedures when compared with their respective open approaches, CO2 pneumoperitoneum may significantly affect local (i.e., infra-abdominal) cellular immunity by reducing regional macrophage function. Results to date are conflicting with regard to the impact of closed and open methods on intraabdominal immunity. Impaired cellular immunity after CO2 pneumoperitoneum may have significant undesirable intra-abdominal effects on tumor surveillance after oncological surgery; however, at present, there is no clinical evidence to support this position. The VATS techniques avoid the use of CO2 insufflation, which may offer some advantages from the immune function perspective over laparoscopic procedures accomplished with CO2 pneumoperitoneum. Better preservation of early postoperative cellular immune function and attenuated disturbance in the inflammatory mediators are likely contributing factors to the clinical benefits that follow laparoscopic surgery and VATS. Larger multi-center randomized trials are needed to confirm the potential benefits of minimal-access surgery on patient survival after cancer surgery. Future research should focus on the effects of minimal-access surgery on other mediators (such as MMP-9, IGFBP-3, IL-12, IL-17, and IL-23) that may be important in tumor cell dissemination, deposition, and propagation in the early postoperative period. Furthermore, additional searches for other factors or mediators, heretofore unrecognized, should be carried out. Such studies will, we hope, increase our knowledge and understanding of the impact of surgery on immune and other physiologic functions.
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Affiliation(s)
- Calvin S H Ng
- Division of Cardiothoracic Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong
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Affiliation(s)
- A Lacy
- Gastrointestinal Surgery Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
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Kaminski JM, Shinohara E, Summers JB, Niermann KJ, Morimoto A, Brousal J. The controversial abscopal effect. Cancer Treat Rev 2005; 31:159-72. [PMID: 15923088 DOI: 10.1016/j.ctrv.2005.03.004] [Citation(s) in RCA: 166] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The abscopal effect is potentially important for tumor control and is mediated through cytokines and/or the immune system, mainly cell-mediated immunity. It results from loss of growth stimulatory and/or immunosuppressive factors from the tumor. Until recently, the abscopal effect referred to the distant effects seen after local radiation therapy. However, the term should now be used interchangeably with distant bystander effect. Through analysis of distant bystander effects of other local therapies, we discuss the poorly understood and researched radiation-induced abscopal effect. Although the abscopal effect has been described in various malignancies, it is a rarely recognized clinical event. The abscopal effect is still extremely controversial with known data that both support and refute the concept.
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Affiliation(s)
- Joseph M Kaminski
- Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, USA
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Jacobi CA, Hartmann J, Ordemann J. Immunologie, minimal invasive Chirurgie und Karzinom. Visc Med 2005. [DOI: 10.1159/000083359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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