|
1
|
Furukawa S, Hiraki M, Kimura N, Okuyama K, Kohya N, Sakai M, Kawaguchi A, Ikubo A, Samejima R. The clinical impact of intraoperative bleeding on peritoneal recurrence after surgery for stage II to III colorectal cancer. Asian J Surg 2024:S1015-9584(24)02314-5. [PMID: 39505635 DOI: 10.1016/j.asjsur.2024.10.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 07/17/2024] [Accepted: 10/04/2024] [Indexed: 11/08/2024] Open
Abstract
BACKGROUND This study aimed to investigate the risk factors for peritoneal recurrence (PR) in patients with stage II to III colorectal cancer who underwent colorectal surgery. METHODS A retrospective study was conducted on 232 patients who underwent colorectal surgery for stage II to III colorectal cancer. Univariate and multivariate analyses were performed to determine risk factors for PR. RESULTS The overall incidence of PR was 8.2 % (19/232). A univariate Cox regression analysis showed that a higher level of carcinoembryonic antigen (CEA) (P = 0.039), higher levels of carbohydrate antigen 19-9 (CA19-9) (P < 0.001), preoperative bowel obstruction (P = 0.011), tumor invasion of T4 category (P = 0.019), lymph node metastasis (P = 0.016), poorly differentiated, mucinous or signet-ring histological type (P = 0.010), larger amount of intraoperative bleeding (P = 0.002), R1 resection (P = 0.003), anastomotic leakage Clavien-Dindo classification (CD) ≥2 (P = 0.018), longer postoperative stay (P = 0.002), and recurrence of other organs preceding disseminated recurrence (P = 0.004) were observed significantly more frequently in patients with PR than in patients without PR. A multivariate Cox regression analysis revealed that poorly differentiated, mucinous, or signet-ring histological type (HR: 5.067, 95 % CI: 1.192-21.534, P = 0.028) and intraoperative bleeding (HR: 1.003, 95 % CI: 1.000-1.005, P = 0.017) were independent risk factors for PR. Peritoneal recurrence-free survival curves generated using the Kaplan-Meier method gradually worsened with increasing intraoperative bleeding (P < 0.001). In addition, the sub-analyses between stage II and stage III and between ≤ cT3 and cT4 also demonstrated that peritoneal recurrence-free survival worsened with increasing intraoperative bleeding. CONCLUSIONS Our findings suggest that histological type, and intraoperative bleeding are risk factors for PR in patients who undergo colorectal surgery for stage II to III colorectal cancer. In particular, peritoneal recurrence is associated with increased intraoperative bleeding.
Collapse
Affiliation(s)
- Shunsuke Furukawa
- Department of Surgery, Japanese Red Cross Society Karatsu Red Cross Hospital, 2430 Watada, Karatsu, Saga, 847-8588, Japan
| | - Masatsugu Hiraki
- Department of Surgery, Japanese Red Cross Society Karatsu Red Cross Hospital, 2430 Watada, Karatsu, Saga, 847-8588, Japan.
| | - Naoya Kimura
- Department of Surgery, Japanese Red Cross Society Karatsu Red Cross Hospital, 2430 Watada, Karatsu, Saga, 847-8588, Japan
| | - Keiichiro Okuyama
- Department of Surgery, Japanese Red Cross Society Karatsu Red Cross Hospital, 2430 Watada, Karatsu, Saga, 847-8588, Japan
| | - Naohiko Kohya
- Department of Surgery, Japanese Red Cross Society Karatsu Red Cross Hospital, 2430 Watada, Karatsu, Saga, 847-8588, Japan
| | - Masashi Sakai
- Department of Surgery, Japanese Red Cross Society Karatsu Red Cross Hospital, 2430 Watada, Karatsu, Saga, 847-8588, Japan
| | - Atsushi Kawaguchi
- Education and Research Center for Community Medicine, Saga University Faculty of Medicine, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Akashi Ikubo
- Department of Surgery, Japanese Red Cross Society Karatsu Red Cross Hospital, 2430 Watada, Karatsu, Saga, 847-8588, Japan
| | - Ryuichiro Samejima
- Department of Surgery, Japanese Red Cross Society Karatsu Red Cross Hospital, 2430 Watada, Karatsu, Saga, 847-8588, Japan
| |
Collapse
|
|
2
|
Zhang C, Zhao S, Wang X. A Postsurgical Prognostic Nomogram for Locally Advanced Rectosigmoid Cancer to Assist in Patient Selection for Adjuvant Chemotherapy. Front Oncol 2022; 11:772482. [PMID: 35004292 PMCID: PMC8739949 DOI: 10.3389/fonc.2021.772482] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 12/06/2021] [Indexed: 11/25/2022] Open
Abstract
Background The perioperative treatment model for locally advanced rectosigmoid junction cancer (LARSC) has not been finalized; whether this model should refer to the treatment model for rectal cancer remains controversial. Methods We screened 10,188 patients with stage II/III rectosigmoid junction adenocarcinoma who underwent surgery between 2004 and 2016 from the National Cancer Institute Surveillance, Epidemiology, and End Results database. Among them, 4,960 did not receive adjuvant chemotherapy, while 5,228 did receive adjuvant chemotherapy. Propensity score matching was used to balance the two groups for confounding factors, and the Kaplan-Meier method and log-rank test were used for survival analysis. Cox proportional hazards regression analysis was used to identify independent prognostic factors and build a predictive nomogram of survival for LARSC. X-tile software was used to divide the patients into three groups (low, medium, and high) according to their risk scores. 726 patients in our hospital were included for external validation. Results LARSC patients did not show a benefit from neoadjuvant radiotherapy (P>0.05). After further excluding patients who received neoadjuvant radiotherapy, multivariate analysis found that age, grade, tumor size, T stage, and log odds of positive lymph nodes were independent prognostic factors for patients without adjuvant chemotherapy and were included in the nomogram. The C-index of the model was 0.690 (95% confidence interval: 0.668–0.712). We divided the patients into low, moderate, and high risk subgroups based on prediction scores of the nomogram. We found that adjuvant chemotherapy did not improve the prognosis of low risk patients, while moderate and high risk patients benefited from adjuvant therapy. External validation data found that moderate, and high risk patients also benefited from AT. Conclusion Direct surgery plus adjuvant chemotherapy may be the best perioperative treatment for LARSC. Moreover, adjuvant chemotherapy is only recommended for moderate and high risk patients as it did not benefit low risk patients.
Collapse
Affiliation(s)
- Chao Zhang
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Shutao Zhao
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Xudong Wang
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, China
| |
Collapse
|
|
3
|
Shi R, Zhao K, Wang T, Yuan J, Zhang D, Xiang W, Qian J, Luo N, Zhou Y, Tang B, Li C, Miao H. 5-aza-2'-deoxycytidine potentiates anti-tumor immunity in colorectal peritoneal metastasis by modulating ABC A9-mediated cholesterol accumulation in macrophages. Theranostics 2022; 12:875-890. [PMID: 34976218 PMCID: PMC8692916 DOI: 10.7150/thno.66420] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 11/23/2021] [Indexed: 02/06/2023] Open
Abstract
Background: 5-aza-2'-deoxycytidine (5Aza), a DNA methyltransferase (DNMT) inhibitor, could activate tumor adaptive immunity to inhibit tumor progression. However, the molecular mechanisms by which 5Aza regulates tumor immune microenvironment are still not fully understood. Methods: The role of 5Aza in immune microenvironment of peritoneal carcinomatosis (PC) of colorectal cancer (CRC) was investigated. The effects of 5Aza on macrophage activation were studied by flow cytometry, real-time PCR, Western blotting assays, and Drug Affinity Responsive Target Stability (DARTS). The effects of 5Aza on tumor immunity were validated in stromal macrophages and T cells from CRC patients. Results: 5Aza could stimulate the activation of macrophages toward an M1-like phenotype and subsequent activation of T cells in premetastatic fat tissues, and ultimately suppress CRC-PC in immune-competent mouse models. Mechanistically, 5Aza stimulated primary mouse macrophages toward to a M1-like phenotype characterized by the increase of p65 phosphorylation and IL-6 expression. Furthermore, we screened and identified ATP-binding cassette transporter A9 (ABC A9) as a binding target of 5Aza. 5Aza induced cholesterol accumulation, p65 phosphorylation and IL-6 expression in an ABC A9-dependent manner. Pharmacological inhibition of NF-κB, or genetic depletion of IL-6 abolished the antitumor effect of 5Aza in mice. In addition, the antitumor effect of 5Aza was synergistically potentiated by conventional chemotherapeutic drugs 5-Fu or OXP. Finally, we validated the reprogramming role of 5Aza in antitumor immunity in stromal macrophages and T cells from CRC patients. Conclusions: Taken together, our findings showed for the first time that 5Aza suppressed CRC-PC by regulating macrophage-dependent T cell activation in premetastatic microenvironment, meanwhile uncovered a DNA methylation-independent mechanism of 5Aza in regulating ABC A9-associated cholesterol metabolism and macrophage activation.
Collapse
|
|
4
|
Choy KT, Yang TWW, Heriot A, Warrier SK, Kong JC. Does rectal tube/transanal stent placement after an anterior resection for rectal cancer reduce anastomotic leak? A systematic review and meta-analysis. Int J Colorectal Dis 2021; 36:1123-1132. [PMID: 33515307 DOI: 10.1007/s00384-021-03851-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/19/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND There is increasing evidence that either a transanal stent (TAS) or rectal tube (RT) can decrease the risk of anastomotic leakage (AL) after anterior resection for rectal cancer, in which a diverting stoma may not be required. OBJECTIVES The aim of this review was to investigate the efficacy and safety of RT/TAS in preventing AL after anterior resections. DATA SOURCES An up-to-date systematic review was performed on the available literature between 2000 and 2020 on PubMed, EMBASE, Medline and Cochrane Library databases. STUDY SELECTION All studies reporting on anterior resections in adults, comparing transanal tube/stent versus non-tube/stent, were analysed. MAIN OUTCOME MEASURE The primary outcome was rates of AL, whereas secondary outcomes compared associated unplanned re-operation for AL and hospital length of stay (LOS). RESULTS Two randomized controlled trials and 13 observational studies were included, with 1714 patients receiving RT/TAS and 1741 patients without. There were 119 (7%) patients with AL in the RT/TAS group compared to 216 (12.3%) patients in the non-RT/TAS group (OR: 0.48, 95% CI: 0.38-0.62, p < 0.001). There were 47 (2.9%) patients with AL complications requiring surgery in the RT/TAS group compared to 132 (8%) patients in the non-RT/TAS group (OR: 0.29, 95% CI: 0.20-0.42, p < 0.001) and no significant difference identified with the standardized mean difference (SMD) favouring the RT/TAS group for hospital LOS (SMD: -0.23, 95% CI: -0.51 to 0.06, p = 0.115). CONCLUSION The use of RT/TAS post restorative anterior resection for rectal cancer should be considered, given the benefits shown from this meta-analysis.
Collapse
Affiliation(s)
- Kay T Choy
- Department of Surgery, Austin Hospital, 145 Studley Rd, Heidelberg, VIC, 3084, Australia.
| | - Tze Wei Wilson Yang
- Department of Colorectal Surgery, Alfred Hospital, Melbourne, Victoria, Australia
| | - Alexander Heriot
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia
| | - Satish K Warrier
- Department of Colorectal Surgery, Alfred Hospital, Melbourne, Victoria, Australia
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia
| | - Joseph C Kong
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia
| |
Collapse
|
|
5
|
Gray M, Marland JRK, Murray AF, Argyle DJ, Potter MA. Predictive and Diagnostic Biomarkers of Anastomotic Leakage: A Precision Medicine Approach for Colorectal Cancer Patients. J Pers Med 2021; 11:471. [PMID: 34070593 PMCID: PMC8229046 DOI: 10.3390/jpm11060471] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 05/19/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
Development of an anastomotic leak (AL) following intestinal surgery for the treatment of colorectal cancers is a life-threatening complication. Failure of the anastomosis to heal correctly can lead to contamination of the abdomen with intestinal contents and the development of peritonitis. The additional care that these patients require is associated with longer hospitalisation stays and increased economic costs. Patients also have higher morbidity and mortality rates and poorer oncological prognosis. Unfortunately, current practices for AL diagnosis are non-specific, which may delay diagnosis and have a negative impact on patient outcome. To overcome these issues, research is continuing to identify AL diagnostic or predictive biomarkers. In this review, we highlight promising candidate biomarkers including ischaemic metabolites, inflammatory markers and bacteria. Although research has focused on the use of blood or peritoneal fluid samples, we describe the use of implantable medical devices that have been designed to measure biomarkers in peri-anastomotic tissue. Biomarkers that can be used in conjunction with clinical status, routine haematological and biochemical analysis and imaging have the potential to help to deliver a precision medicine package that could significantly enhance a patient's post-operative care and improve outcomes. Although no AL biomarker has yet been validated in large-scale clinical trials, there is confidence that personalised medicine, through biomarker analysis, could be realised for colorectal cancer intestinal resection and anastomosis patients in the years to come.
Collapse
Affiliation(s)
- Mark Gray
- The Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush, Roslin, Midlothian, Edinburgh EH25 9RG, UK;
| | - Jamie R. K. Marland
- School of Engineering, Institute for Integrated Micro and Nano Systems, University of Edinburgh, Scottish Microelectronics Centre, King’s Buildings, Edinburgh EH9 3FF, UK;
| | - Alan F. Murray
- School of Engineering, Institute for Bioengineering, University of Edinburgh, Faraday Building, The King’s Buildings, Edinburgh EH9 3DW, UK;
| | - David J. Argyle
- The Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush, Roslin, Midlothian, Edinburgh EH25 9RG, UK;
| | - Mark A. Potter
- Department of Surgery, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK;
| |
Collapse
|
|
6
|
Breuer E, Hebeisen M, Schneider MA, Roth L, Pauli C, Frischer-Ordu K, Eden J, Pache B, Steffen T, Hübner M, Villeneuve L, Kepenekian V, Passot G, Gertsch P, Gupta A, Glehen O, Lehmann K. Site of Recurrence and Survival After Surgery for Colorectal Peritoneal Metastasis. J Natl Cancer Inst 2021; 113:1027-1035. [PMID: 33484560 DOI: 10.1093/jnci/djab001] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 11/23/2020] [Accepted: 01/04/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Multimodal treatment, including systemic treatment and surgery, improved the prognosis of peritoneal metastasis (PM). Despite all efforts, recurrence rates remain high, and little data are available about clinical behavior or molecular patterns of PM in comparison to hematogenous metastasis. Here, we aimed to analyze recurrence patterns after multimodal treatment for PM from colorectal cancer. METHODS Patients with colorectal PM undergoing multimodal treatment including systemic chemotherapy and cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) between 2005 and 2017 at 4 centers were analyzed retrospectively. RESULTS A total of 505 patients undergoing CRS/HIPEC were analyzed. Of the patients, 82.1% received preoperative chemotherapy. Median peritoneal cancer index was 6 (interquartile range = 3-11). Median disease-free and overall survival was 12 (95% confidence interval [CI] = 11 to 14) months and 51 (95% CI = 43 to 62) months, respectively. Disease recurred in 361 (71.5%) patients, presenting as isolated peritoneal recurrence in 24.6%, isolated hematogenous recurrence in 28.3%, and mixed recurrence in 13.9% of patients. Recurrence to the peritoneum was associated with an impaired time from recurrence to death of 21 (95% CI = 18 to 31) months for isolated peritoneal and 22 (95% CI = 16 to 30) months for mixed recurrence, compared with 43 (95% CI = 31 to >121) months for hematogenous recurrence (hazard ratio [HR] = 1.79, 95% CI = 1.27 to 2.53; P = .001; and HR = 2.44, 95% CI = 1.61 to 3.79; P < .001). On multiple logistic regression analysis, RAS mutational status (odds ratio [OR] = 2.42, 95% CI = 1.11 to 5.47; P = .03) and positive nodal stage of the primary (OR = 3.88, 95% CI = 1.40 to 11.86; P = .01) were identified as predictive factors for peritoneal recurrence. CONCLUSIONS This study highlights the heterogeneity of peritoneal metastasis in patients with colorectal cancer. Recurrent peritoneal metastasis after radical treatment represents a more aggressive subset of metastatic colorectal cancer.
Collapse
Affiliation(s)
- Eva Breuer
- Department of Surgery & Transplantation, Surgical Oncology Research Laboratory, University Hospital of Zurich, Zurich, Switzerland
| | - Monika Hebeisen
- Department of Biostatistics at Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland
| | - Marcel André Schneider
- Department of Surgery & Transplantation, Surgical Oncology Research Laboratory, University Hospital of Zurich, Zurich, Switzerland
| | - Lilian Roth
- Department of Surgery & Transplantation, Surgical Oncology Research Laboratory, University Hospital of Zurich, Zurich, Switzerland
| | - Chantal Pauli
- Department of Pathology and Molecular Pathology, University Hospital Zürich, Zurich, Switzerland.,University of Zurich (UZH), Zurich, Switzerland
| | - Katharina Frischer-Ordu
- Department of Pathology and Molecular Pathology, University Hospital Zürich, Zurich, Switzerland
| | - Janina Eden
- Department of Surgery, Cantonal Hospital of St Gallen, Switzerland
| | - Basile Pache
- Department of Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland
| | - Thomas Steffen
- Department of Surgery, Cantonal Hospital of St Gallen, Switzerland
| | - Martin Hübner
- Department of Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland
| | - Laurent Villeneuve
- Department of Surgical Oncology, University Hospital of Lyon, Lyon, France
| | - Vahan Kepenekian
- Department of Surgical Oncology, University Hospital of Lyon, Lyon, France
| | - Guillaume Passot
- Department of Surgical Oncology, University Hospital of Lyon, Lyon, France
| | - Philippe Gertsch
- Department of Surgery & Transplantation, Surgical Oncology Research Laboratory, University Hospital of Zurich, Zurich, Switzerland
| | - Anurag Gupta
- Department of Surgery & Transplantation, Surgical Oncology Research Laboratory, University Hospital of Zurich, Zurich, Switzerland
| | - Olivier Glehen
- Department of Surgical Oncology, University Hospital of Lyon, Lyon, France
| | - Kuno Lehmann
- Department of Surgery & Transplantation, Surgical Oncology Research Laboratory, University Hospital of Zurich, Zurich, Switzerland.,University of Zurich (UZH), Zurich, Switzerland
| |
Collapse
|
|
7
|
Shi R, Xiang W, Kang X, Zhang L, Wang J, Miao H, He F. Alteration of Adaptive Immunity in a Colorectal Peritoneal Carcinomatosis Model. J Cancer 2019; 10:367-377. [PMID: 30719130 PMCID: PMC6360308 DOI: 10.7150/jca.27947] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Accepted: 10/03/2018] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) usually gives rise to transcoelomic spread and ultimately causes peritoneal carcinomatosis (PC). However, mechanism studies, especially the immunological basis of colorectal PC, are rarely revealed due to lack of a suitable PC model. Here we selected a mouse colorectal cancer cell line MC-38 for intraperitoneal inoculation in the C57BL/6 mice to mimic the development of colorectal PC. We demonstrated that the injected CRC cells preferentially and rapidly migrated and colonized in the visceral fat tissues, but not in other visceral organs. With flow cytometric analysis, we found the proportions of spleen T cells and B cells were not affected by PC progression, while the ratios of blood CD4+ and CD8+ T cells were largely influenced. Especially, the quantity or activity of CD4+ and CD8+ T cells in visceral fats were intimately regulated by PC development. Taken together, we successfully constructed a colorectal PC model in immune-competent mice and revealed the alteration of adaptive immunity in PC development. Our study might potentiate the research and therapy strategies of colorectal PC.
Collapse
Affiliation(s)
- Rongchen Shi
- Department of Biochemistry and Molecular Biology, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Wei Xiang
- Department of Biochemistry and Molecular Biology, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Xia Kang
- Department of Biochemistry and Molecular Biology, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Lili Zhang
- Department of Military Psychology, School of Psychology, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Jinping Wang
- Department of Neurology, Chongqing Emergency Medical Center, Chongqing 400014, China
| | - Hongming Miao
- Department of Biochemistry and Molecular Biology, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Fengtian He
- Department of Biochemistry and Molecular Biology, Third Military Medical University (Army Medical University), Chongqing 400038, China
| |
Collapse
|
|
8
|
Ramphal W, Boeding JRE, Gobardhan PD, Rutten HJT, de Winter LJMB, Crolla RMPH, Schreinemakers JMJ. Oncologic outcome and recurrence rate following anastomotic leakage after curative resection for colorectal cancer. Surg Oncol 2018; 27:730-736. [PMID: 30449500 DOI: 10.1016/j.suronc.2018.10.003] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Revised: 08/31/2018] [Accepted: 10/01/2018] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Anastomotic leakage is one of the most severe early complications after colorectal surgery, and it is associated with a high reoperation rate-, and increased in short-term morbidity and mortality rates. It remains unclear whether anastomotic leakage is associated with poor oncologic outcomes. The aim of this study was to determine the impacts of anastomotic leakage on long-term oncologic outcomes, disease-free survival and overall mortality in patients who underwent curative surgery for colorectal cancer. METHODS This single-centre, retrospective, observational cohort study included patients who underwent curative surgery for colorectal cancer between 2005 and 2015 and who had a primary anastomosis. Survival- and multivariate cox regression analyses were performed to adjust for confounding. RESULTS A total of 1984 patients had a primary anastomosis after surgery. The overall incidence of anastomotic leakage was 7.5%; 19 patients were excluded because they were lost to follow-up. Of the remaining 1965 patients, 41 (2.1%) developed local recurrence associated with anastomotic leakage [adjusted hazard ratio (HR) = 2.25; 95% confidence interval (CI) 1.14-5.29; P = 0.03]. Distant recurrence developed in 291(14.8%) patients with no association with anastomotic leakage [adjusted HR = 1.30 (95% CI: 0.85-1.97) P = 0.23]. Anastomotic leakage was associated with increased long-term mortality [adjusted HR = 1.69 (95% CI 1.32-2.18) P < 0.01]. Five year disease-free survival was significantly decreased in patients with anastomotic leakage, (log rank test P < 0.01). CONCLUSION Anastomotic leakage was significantly associated with increased rates of local recurrence, disease free-survival and overall mortality. Associations of anastomotic leakage with distant recurrence was not found.
Collapse
Affiliation(s)
- Winesh Ramphal
- Department of Surgery, Amphia Hospital Breda, the Netherlands.
| | | | | | - Harm J T Rutten
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands; GROW: School of Oncology and Developmental Biology, University of Maastricht, Maastricht, the Netherlands
| | | | | | | |
Collapse
|
|
9
|
Hornung M, Werner JM, Schlitt HJ. Applications of hyperthermic intraperitoneal chemotherapy for metastatic colorectal cancer. Expert Rev Anticancer Ther 2017; 17:841-850. [PMID: 28715968 DOI: 10.1080/14737140.2017.1357470] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
INTRODUCTION Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) plays a pivotal role in the current treatment of peritoneal carcinomatosis (PC) from colorectal cancer (CRC). Since the first demonstration, benefits for patients and especially an increase in survival have been described. In recent years, feasibility, efficacy and safety of HIPEC have been improved and progress has been made in understanding its oncological mechanism. Areas covered: In this article, leading publications have been reviewed including clinical trials to describe the clinical presentation of PC due to CRC and present recent evidence of the CRS/HIPEC procedure. The surgical approach including evaluation of the extent of PC is described and, in addition, the article reports about different HIPEC techniques as well as several protocols. Furthermore, the development and prognostic benefit of the combination of intraperitoneal and intravenous chemotherapy are outlined. Consideration has been given in particular to patient selection and the use of HIPEC if complete cytoreduction is not feasible. Expert commentary: The CRS/HIPEC procedure represents a curative approach to treat patients with PC from CRC. However, surgical skills and the HIPEC technique still require specialized oncological centers.
Collapse
Affiliation(s)
- Matthias Hornung
- a Department of Surgery , University of Regensburg , Regensburg , Germany
| | - Jens M Werner
- a Department of Surgery , University of Regensburg , Regensburg , Germany
| | - Hans J Schlitt
- a Department of Surgery , University of Regensburg , Regensburg , Germany
| |
Collapse
|
|
10
|
Murono K, Ishihara S, Kawai K, Kaneko M, Sasaki K, Otani K, Yasuda K, Nishikawa T, Tanaka T, Kiyomatsu T, Hata K, Nozawa H, Satoh Y, Kurihara M, Yatomi Y, Watanabe T. Significance of carcinoembryonic antigen mRNA in peritoneal lavage determined by transcription-reverse transcription concerted method in patients with low rectal cancer. Asian J Surg 2017; 41:321-327. [PMID: 28291565 DOI: 10.1016/j.asjsur.2017.01.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Revised: 12/20/2016] [Accepted: 01/26/2017] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND/OBJECTIVE Positive carcinoembryonic antigen (CEA) messenger RNA (mRNA) in peritoneal lavage is associated with poor prognosis in patients with colon cancer. However, there are no reports about rectal cancer. Therefore we aimed to evaluate the frequency of positive CEA mRNA in peritoneal lavage and the significance of CEA mRNA in patients with low rectal cancer. METHODS A total of 55 patients with low rectal cancer who received curative surgical resection were enrolled. CEA mRNA in peritoneal lavage was measured using the transcription-reverse transcription concerted method, a quantitative RNA amplification method. The correlation between CEA mRNA and overall and peritoneal recurrence-free survival was evaluated. RESULTS Among 55 patients, 6 (10.9%) had positive CEA mRNA in peritoneal lavage. Patients with positive CEA mRNA resulted in significantly higher recurrence rate than those with negative CEA mRNA (p=0.007). Similarly, the local recurrence rate was significantly higher in the positive CEA mRNA group than in the negative CEA mRNA group (p=0.0009). Lymph node metastasis and positive CEA mRNA were independent risk factors for overall and local recurrence. CONCLUSION Positive CEA mRNA in low rectal cancer is a factor that predisposes patients to a high risk for overall recurrence, especially for local recurrence.
Collapse
Affiliation(s)
- Koji Murono
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
| | - Soichiro Ishihara
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan
| | - Kazushige Kawai
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan
| | - Manabu Kaneko
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan
| | - Kazuhito Sasaki
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan
| | - Kensuke Otani
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan
| | - Koji Yasuda
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan
| | - Takeshi Nishikawa
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan
| | - Toshiaki Tanaka
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan
| | - Tomomichi Kiyomatsu
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan
| | - Keisuke Hata
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan
| | - Hiroaki Nozawa
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan
| | - Yumiko Satoh
- Department of Clinical Laboratory, Faculty of Medicine, University of Tokyo, Tokyo, Japan
| | - Makiko Kurihara
- Department of Clinical Laboratory, Faculty of Medicine, University of Tokyo, Tokyo, Japan
| | - Yutaka Yatomi
- Department of Clinical Laboratory, Faculty of Medicine, University of Tokyo, Tokyo, Japan
| | - Toshiaki Watanabe
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan
| |
Collapse
|
|
11
|
Kim NK, Kim YW, Han YD, Cho MS, Hur H, Min BS, Lee KY. Complete mesocolic excision and central vascular ligation for colon cancer: Principle, anatomy, surgical technique, and outcomes. Surg Oncol 2016; 25:252-62. [PMID: 27566031 DOI: 10.1016/j.suronc.2016.05.009] [Citation(s) in RCA: 75] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Accepted: 05/19/2016] [Indexed: 12/15/2022]
Abstract
Classic colon cancer surgery refers to a wide resection of the tumor-bearing segment and the lymphatics draining along the named artery. The concept of TME has been applied to colon cancer and complete mesocolic excision (CME) in conjuction with central vascular ligation (CVL) has been introduced as the surgical treatment for colon cancer. Here, we discuss appropriate CME procedure with regard to the oncologic backgrounds, essential components, applied anatomy, laparoscopic technique, short-term, and oncologic outcomes. The introduction of CME has improved oncologic outcomes greatly in patients with colon cancer. The improved outcomes with CME can be attributed to underlying sound oncologic principles such as dissection through the proper plane of mesocolic excision, central vascular ligation, and sufficient length of proximal and distal margins. Thereby, CME technique can achieve en bloc removal of the diseased lesion with the increased amount of the colonic mesentery even though the length of for both bowel and mesentery resection remains a matter of debate. CME is a technically demanding operation thus, comprehensive understanding of the applied vascular anatomy is essential for successful CME. Favorable outcomes of open CME have been replicated with a laparoscopic approach. In future perspective, incorporating a structured education program on minimally invasive (laparoscopy or robot) CME would be beneficial.
Collapse
Affiliation(s)
- Nam Kyu Kim
- Department of Surgery, Division of Colorectal Surgery, Yonsei University College of Medicine, Seoul, South Korea.
| | - Young Wan Kim
- Department of Surgery, Division of Colorectal Surgery, Yonsei University Wonju College of Medicine, Wonju, South Korea
| | - Yoon Dae Han
- Department of Surgery, Division of Colorectal Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - Min Soo Cho
- Department of Surgery, Division of Colorectal Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - Hyuk Hur
- Department of Surgery, Division of Colorectal Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - Byung Soh Min
- Department of Surgery, Division of Colorectal Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - Kang Young Lee
- Department of Surgery, Division of Colorectal Surgery, Yonsei University College of Medicine, Seoul, South Korea
| |
Collapse
|
|
12
|
Anastomotic Leaks After Restorative Resections for Rectal Cancer Compromise Cancer Outcomes and Survival. Dis Colon Rectum 2016; 59:236-44. [PMID: 26855399 DOI: 10.1097/dcr.0000000000000554] [Citation(s) in RCA: 96] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Anastomotic leaks after restorative resections for rectal cancer may lead to worse long-term outcomes. OBJECTIVE The purpose of this study was to evaluate the best current evidence assessing anastomotic leaks in rectal cancer resections with curative intent and their impact on survival and cancer recurrence. DATA SOURCES A meta-analysis was performed using MEDLINE, EMBASE, and Cochrane search engines for relevant studies published between January 1982 and January 2015. STUDY SELECTION Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology was used to screen and select relevant studies for the review using key words "colorectal surgery; colorectal neoplasm; rectal neoplasm" and "anastomotic leak." INTERVENTION Anastomotic leak groups were compared with nonanastomotic leak groups. MAIN OUTCOME MEASURES ORs were calculated from binary data for local recurrence, distant recurrence, and cancer-specific mortality. A random-effects model was then used to calculate pooled ORs with 95% CIs. RESULTS Eleven studies with 13,655 patients met the inclusion criteria. This included 5 prospective cohort and 6 retrospective cohort studies. Median follow-up was 60 months. Higher cancer-specific mortality was noted in the leak group with an OR of 1.30 (95% CI, 1.04-1.62; p < 0.05). Local recurrences were more likely in rectal cancer resections complicated by anastomotic leaks (OR = 1.61 (95% CI, 1.25-2.09); p < 0.001). Distant recurrence was not more likely in the anastomotic leak group (OR = 1.07 (95% CI, 0.87-1.33); p = 0.52). LIMITATIONS All 11 studies are level 3 evidence cohort studies. Additional sensitivity analyses were performed to minimize cross-study heterogeneity. CONCLUSIONS Anastomotic leaks after restorative resections for rectal cancer adversely impact cancer-specific mortality and local recurrence.
Collapse
|
|
13
|
Murono K, Kazama S, Yamaguchi H, Kawai K, Ishihara S, Sunami E, Kitayama J, Satoh Y, Kurihara M, Yatomi Y, Watanabe T. Detection of carcinoembryonic antigen mRNA in peritoneal lavage by the transcription-reverse transcription concerted method indicates poor prognosis in patients with stage II and III colon cancer. Surgery 2014; 157:322-30. [PMID: 25311262 DOI: 10.1016/j.surg.2014.09.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2014] [Revised: 08/27/2014] [Accepted: 09/05/2014] [Indexed: 12/17/2022]
Abstract
BACKGROUND Peritoneal dissemination and positive peritoneal lavage cytology are associated with poor prognosis in colorectal cancer. Carcinoembryonic antigen (CEA) messenger RNA (mRNA) is often used as a marker to detect micrometastases. We aimed to evaluate the prognostic significance of CEA mRNA in the peritoneal lavage of colon cancer patients. METHODS Colon cancer patients (n = 201) who underwent curative operative resection between August 2009 and February 2013 were enrolled. CEA mRNA in peritoneal lavage was measured using the transcription-reverse transcription concerted method, a quantitative RNA amplification method. The correlation between CEA mRNA and overall and peritoneal recurrence-free survival was evaluated. RESULTS Positive CEA mRNA in peritoneal lavage was an independent risk factor for overall recurrence-free survival in colon cancer (P < .0001). Positive CEA mRNA was a risk factor for poorer overall recurrence in stage II and III patients (P = .04 and P = .02, respectively). Moreover, among stage III patients with positive CEA mRNA, the postoperative chemotherapy group had significantly lower overall and peritoneal recurrence rates than the no postoperative chemotherapy group (P = .001). CONCLUSION Positive CEA mRNA in peritoneal lavage was associated with high overall recurrence rates in stage II and III colon cancer. Further study is necessary to determinate the efficacy of aggressive postoperative chemotherapy for stage II and III colon cancer patients with positive CEA mRNA.
Collapse
Affiliation(s)
- Koji Murono
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
| | - Shinsuke Kazama
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hironori Yamaguchi
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazushige Kawai
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Soichiro Ishihara
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Eiji Sunami
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Joji Kitayama
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yumiko Satoh
- Department of Clinical Laboratory, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Makiko Kurihara
- Department of Clinical Laboratory, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yutaka Yatomi
- Department of Clinical Laboratory, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Toshiaki Watanabe
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| |
Collapse
|
|
14
|
Passot G, Mohkam K, Cotte E, Glehen O. Intra-operative peritoneal lavage for colorectal cancer. World J Gastroenterol 2014; 20:1935-9. [PMID: 24616569 PMCID: PMC3934463 DOI: 10.3748/wjg.v20.i8.1935] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Revised: 11/28/2013] [Accepted: 01/06/2014] [Indexed: 02/06/2023] Open
Abstract
Free cancer cells can be detected in peritoneal fluid at the time of colorectal surgery. Peritoneal lavage in colorectal surgery for cancer is not used in routine, and the prognostic significance of intraperitoneal free cancer cells (IPCC) remains unclear. Data concerning the technique of peritoneal lavage to detect IPCC and its timing regarding colorectal resection are scarce. However, positive IPCC might be the first step of peritoneal spread in colorectal cancers, which could lead to early specific treatments. Because of the important heterogeneity of IPCC determination in reported studies, no treatment have been proposed to patients with positive IPCC. Herein, we provide an overview of IPCC detection and its impact on recurrence and survival, and we suggest further multi-institutional studies to evaluate new treatment strategies.
Collapse
|
|
15
|
Histologic features and cytologic techniques that aid pathologic stage assessment of colonic adenocarcinoma. Am J Surg Pathol 2013; 37:1252-8. [PMID: 23774176 DOI: 10.1097/pas.0b013e3182960e7c] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Cancer involvement of the colonic serosa is designated pT4a by the American Joint Committee on Cancer Staging Manual, 7th edition. The manual defines criteria for pT4a as either tumor penetration of the serosa or comingling of cancer cells and mesothelial cells in histologic sections. Unfortunately, the pT4a grouping is inconsistently applied, because these guidelines are overly limited: fibroinflammatory changes near the serosa may be associated with peritoneal metastases even in the absence of overt peritoneal penetration. Thus, reliable ancillary techniques for detecting serosal penetration by the tumor and accurate criteria for stage assessment are needed. We evaluated the utility of cytologic preparations in determining tumor stage by comparing results of serosal scrape cytology with histologic stage assessment of 120 colon cancer resection specimens. We correlated our findings with the presence and type of inflammatory changes near the serosa to determine which, if any, are reliable indicators of peritoneal penetration. Cytologic smears from all pT1 and pT2 tumors were negative for carcinoma. However, 13 (19%) pT3 tumors showed cancer in cytologic smears, all of which were deeply invasive. In fact, 46% of pT3 cancers present ≤1 mm from a serosal tissue reaction were associated with cancer in cytologic preparations from the serosa, which was comparable to pT4a tumors (55%). We conclude that cytologic smears improve detection of peritoneal penetration among pT3 tumors compared with histology alone. Tumors close (≤1 mm) to a fibroinflammatory tissue reaction on the serosa are likely associated with peritoneal involvement by cancer. Peritumoral abscesses that communicate with the serosa and hemorrhage or fibrin on the serosa also predict cancer involvement of the peritoneum. The presence of these findings among deeply invasive cancers should prompt their classification as pT4a lesions.
Collapse
|
|
16
|
Akagi Y, Kinugasa T, Adachi Y, Shirouzu K. Prognostic significance of isolated tumor cells in patients with colorectal cancer in recent 10-year studies. Mol Clin Oncol 2013; 1:582-592. [PMID: 24649214 DOI: 10.3892/mco.2013.116] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2012] [Accepted: 04/18/2013] [Indexed: 12/14/2022] Open
Abstract
Circulating tumor cells (CTCs) that detach from the primary tumor and move into the circulation are detected in patients with metastatic cancer. The discovery of such cancer cells has been used as a predictor of recurrence and prognosis, although a consensus regarding such applications has not been reached. Peritoneal cytology may be used for identifying high risk of recurrence or mortality, whereas the intraoperative presence of tumor cells in drainage veins, bone marrow, or the liver is not always useful for evaluating the prognosis. The reported positive rate for tumor cells in the peripheral blood of patients with colorectal cancer, including metastasis, has varied from 10 to 80%; however, numerous studies have demonstrated significant differences in the recurrence and mortality rates between patients with and without isolated tumor cells (ITCs) in the peripheral blood. However, the clinical significance of CTCs as an absolute prognostic factor has not been elucidated, since the measurement methodologies and/or the number of cases differed between the studies. Future prospective studies including larger patient populations may elucidate the utility of routine detection of ITCs in daily practice.
Collapse
Affiliation(s)
- Yoshito Akagi
- Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Tetsushi Kinugasa
- Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Yosuke Adachi
- Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Kazuo Shirouzu
- Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| |
Collapse
|
|
17
|
Lack of prognostic significance of conventional peritoneal cytology in colorectal and gastric cancers: results of EVOCAPE 2 multicentre prospective study. Eur J Surg Oncol 2013; 39:707-14. [PMID: 23601984 DOI: 10.1016/j.ejso.2013.03.021] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2012] [Revised: 02/28/2013] [Accepted: 03/25/2013] [Indexed: 01/01/2023] Open
Abstract
AIM In digestive cancers, the prognostic significance of intraperitoneal free cancer cells remains unclear (IPCC). The main objective of this study was to assess the prognostic significance of IPCC in colorectal and gastric adenocarcinoma. The secondary objectives were to evaluate the predictive significance of IPCC for the development of peritoneal carcinomatosis (PC) and to evaluate the prevalence of synchronous PC and IPCC. METHODS This was a prospective multicentre study. All patients undergoing surgery for a digestive tract cancer had peritoneal cytology taken. Patients with gastric and colorectal cancer with no residual tumour after surgery and no evidence of PC were followed-up for 2 years. The primary end point was overall survival. RESULTS Between 2002 and 2007, 1364 patients were enrolled and 956 were followed-up over 2 years. Prevalence of IPCC was 5.7% in colon cancer, 0.6% in rectal cancer and 19.5% in gastric cancer. The overall 2-year survival rate for patients with IPCC was 34.7% versus 86.8% for patients with negative cytology (p<0.0001). By multivariate analysis, IPCC was not an independent prognostic factor. No relationship between cytology and recurrence was found. CONCLUSION The presence of IPCC was not an independent prognostic and didn't add any additional prognostic information to the usual prognostic factors related to the tumour (pTNM and differentiation). Moreover the presence of IPCC detected with this method didn't appear to predict development of PC. Peritoneal cytology using conventional staining doesn't seem to be a useful tool for the staging of colorectal and gastric cancers.
Collapse
|
|
18
|
Bosanquet DC, Harris DA, Evans MD, Beynon J. Systematic review and meta-analysis of intraoperative peritoneal lavage for colorectal cancer staging. Br J Surg 2013; 100:853-62. [PMID: 23536330 DOI: 10.1002/bjs.9118] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/06/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND Intraperitoneal cancer cells are detectable at the time of colorectal cancer resection in some patients. The significance of this, particularly in patients with no other adverse prognostic features, is poorly defined. Consequently peritoneal lavage is not part of routine practice during colorectal cancer resection, in contrast with other abdominal malignancies. The aim of this systematic review was to determine the effect of positive intraoperative peritoneal cytology on cancer-specific outcomes in colorectal cancer. METHODS A systematic review of key electronic journal databases was undertaken using the search terms 'peritoneal cytology' and 'colorectal' from 1980 to 2012. Studies including patients with frank peritoneal metastasis were excluded. Meta-analysis for overall survival, local/peritoneal recurrence and overall recurrence was performed. RESULTS Twelve cohort studies (2580 patients) met the inclusion criteria. The weighted mean yield was 11·6 (range 2·2-41) per cent. Yield rates were dependent on timing of sampling (before resection, 11·8 per cent; after resection, 13·2 per cent) and detection methods used (cytopathology, 8·4 per cent; immunocytochemistry, 28·3 per cent; polymerase chain reaction, 14·5 per cent). Meta-analysis showed that positive peritoneal lavage predicted worse overall survival (odds ratio (OR) 4·26, 95 per cent confidence interval 2·86 to 6·36; P < 0·001), local/peritoneal recurrence (OR 6·57, 2·30 to 18·79; P < 0·001) and overall recurrence (OR 4·02, 2·24 to 7·22; P < 0·001). CONCLUSION Evidence of intraoperative peritoneal tumour cells at colorectal cancer resection is predictive of adverse cancer outcomes.
Collapse
Affiliation(s)
- D C Bosanquet
- Department of Colorectal Surgery, Abertawe Bro Morgannwg University Trust, Singleton Hospital, Sketty Lane, Swansea, SA2 8QA, UK
| | | | | | | |
Collapse
|
|
19
|
Hompes D, Tiek J, Wolthuis A, Fieuws S, Penninckx F, Van Cutsem E, D'Hoore A. HIPEC in T4a colon cancer: a defendable treatment to improve oncologic outcome? Ann Oncol 2012; 23:3123-3129. [PMID: 22831982 DOI: 10.1093/annonc/mds173] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Adequate estimation of the potential benefits of 'adjuvant' hyperthermia and intraperitoneal chemotherapy (HIPEC) in T4 patients through assessment of the burden of peritoneal carcinomatosis (PC) in T4 tumors and the risk of PC as the only metastatic site. PATIENTS AND METHODS Analysis of prospectively collected data on patients who underwent surgery for colon cancer (Jan 2004-Jan 2007). RESULTS About 379 patients (M/F = 204/175) were included, with a median age of 71.8 years (range 35.4-95.0): 39 stage I, 126 stage II, 89 stage III, 116 stage IV disease (+9 with unknown stage). The median follow-up was 34.8months [range 0.0-79.4]. The 3- and 5-year overall survival rates (OS) were 68.4% (95% confidence interval (CI) 63.9%-72.4%) and 60.3% (95%CI 55.6%-64.7%). Relapse analysis was restricted to stages II-III T3 (N = 154) and T4 tumors (N = 19) with complete relapse data, of which 13.2% developed PC. PC has a detrimental effect on OS [HR 6.3 (95%CI: 3.1-13.0, P < 0.0001)]. 50% of T4a and 20% of T4b developed PC. The 1- and 3-year PC percentage was significantly lower for T3 (4.5% and 9.3%) than T4 tumors (15.6% and 36.7%) (P = 0.008). PC was the only metastatic site in 3/15 T3 [proportion 0.20, 95%CI (0.043-0.481)] and 5/8 T4 tumors with PC [proportion 0.625, 95%CI (0.245-0.915)] (P = 0.071). CONCLUSIONS T4a colon tumors have a significantly higher risk of developing PC. Twenty-five percent (5/19) of stages II-III T4 tumors develop PC as the only metastatic site. This could define the possible window of opportunity for adjuvant HIPEC to prevent PC.
Collapse
Affiliation(s)
- D Hompes
- Department of Abdominal Surgery, University Hospitals Gasthuisberg, Leuven.
| | - J Tiek
- Department of Abdominal Surgery, University Hospitals Gasthuisberg, Leuven
| | - A Wolthuis
- Department of Abdominal Surgery, University Hospitals Gasthuisberg, Leuven
| | - S Fieuws
- Department of Digestive Oncology, University Hospitals Gasthuisberg, Leuven and Universiteit Hasselt, Leuven, Belgium
| | - F Penninckx
- Department of Abdominal Surgery, University Hospitals Gasthuisberg, Leuven
| | - E Van Cutsem
- Department of Digestive Oncology, I-Biostat, Katholieke Universiteit Leuven and Universiteit Hasselt
| | - A D'Hoore
- Department of Abdominal Surgery, University Hospitals Gasthuisberg, Leuven
| |
Collapse
|
|
20
|
Belt EJT, Stockmann HBAC, Abis GSA, de Boer JM, de Lange-de Klerk ESM, van Egmond M, Meijer GA, Oosterling SJ. Peri-operative bowel perforation in early stage colon cancer is associated with an adverse oncological outcome. J Gastrointest Surg 2012; 16:2260-6. [PMID: 23093449 DOI: 10.1007/s11605-012-2053-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2012] [Accepted: 10/11/2012] [Indexed: 01/31/2023]
Abstract
BACKGROUND The presence of an inflammatory response resulting from bowel perforation or anastomotic leakage has been suggested to enhance recurrence rates in colorectal cancer patients. Currently, it is unknown if bowel perforation or anastomotic leakage has prognostic significance in early stage colon cancer patients. In this study, the impact of peri-operative bowel perforation including anastomotic leakage on disease-free survival of stage I/II colon cancer patients was investigated. METHODS Prospective follow up data of 448 patients with stages I/II colon cancer that underwent resection were included. Patients who died within 3 months after initial surgery were excluded. RESULTS Median follow up was 56.0 months. Patients with peri-operative bowel perforation (n = 25) had a higher recurrence rate compared to patients without perforation (n = 423), 36.0 % vs. 16.1 % (p = 0.01). Disease-free survival was significantly worse for the perforation group compared to patients without perforation (p = 0.004). Multivariate analysis including T-stage, histological grade, and adjuvant chemotherapy showed peri-operative bowel perforation to be an independent factor significantly associated with disease recurrence (odds ratio, 2.7; 95 % CI, 1.1-6.7). CONCLUSION Peri-operative bowel perforation is associated with increased recurrence rates and impaired disease-free survival in early-stage colon cancer patients.
Collapse
Affiliation(s)
- E J T Belt
- Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands
| | | | | | | | | | | | | | | |
Collapse
|
|
21
|
Sugarbaker PH, Sammartino P, Tentes AA. Proactive management of peritoneal metastases from colorectal cancer: the next logical step toward optimal locoregional control. COLORECTAL CANCER 2012; 1:115-123. [DOI: 10.2217/crc.12.8] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
SUMMARY Although surgery for colorectal cancer has improved over the last decade, locoregional recurrence and peritoneal metastases continue as a mechanism of surgical treatment failure in 10–20% of patients. These patients have a dismal prognosis. Clinical information is available in order to identify patients who are at high risk for locoregional recurrence and peritoneal metastases. These patients, once identified, should be offered new treatment options shown to be of benefit in selected patients. Using perioperative chemotherapy at the time of colorectal cancer resection improves locoregional control and diminishes peritoneal metastases. Also, in patients at high risk, a proactive second-look surgery utilizing peritonectomy and hyperthermic intraperitoneal chemotherapy is of benefit, with reasonable morbidity and mortality.
Collapse
Affiliation(s)
- Paul H Sugarbaker
- Washington Cancer Institute, 106 Irving Street, NW, Suite 3900, Washington, DC 20010, USA
| | - Paolo Sammartino
- Department of Surgery, University of Rome La Sapienza, Rome, Italy
| | | |
Collapse
|
|
22
|
Abstract
Peritoneal carcinomatosis occurs in patients with advanced gastrointestinal and gynecological malignancies and also in patients who experience recurrence after treatment failure of the primary tumor. Malignant disease in the peritoneal cavity is a morbid and significant predictor of a diminished survival in a cancer patient. Systemic chemotherapy alone will not be adequate to palliate or treat patients with peritoneal carcinomatosis. Cytoreductive surgery is a new surgical technique that is performed using peritonectomy procedures to allow total eradication of peritoneal tumors. Intraperitoneal chemotherapy regimens such as intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC) are effective adjuvant treatment to treat the minimal residual disease after cytoreductive surgery to reduce the risk of locoregional recurrence. A substantial body of evidence available in the current literature has documented the survival benefits of combining cytoreductive surgery and intraperitoneal chemotherapy to treat a previously fatal phase of malignancy. This review provides a summary of the developments in the understanding and treatment of peritoneal surface malignancy from colorectal cancer.
Collapse
Affiliation(s)
- Terence C Chua
- UNSW Department of Surgery, Hepatobiliary and Surgical Oncology Unit, St George Hospital, Sydney, Australia
| | | | | |
Collapse
|
|
23
|
Klaver Y, Lemmens V, Creemers G, Rutten H, Nienhuijs S, de Hingh I. Population-based survival of patients with peritoneal carcinomatosis from colorectal origin in the era of increasing use of palliative chemotherapy. Ann Oncol 2011; 22:2250-6. [DOI: 10.1093/annonc/mdq762] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
|
|
24
|
Piaton E, Villeneuve L, Maurice C, Paulin C, Cottier M, Fontanière B, Salle M, Seigneurin D, Vancina S, Decullier E, Gilly FN, Cotte E. Intraperitoneal free cancer cells in non-gynaecological adenocarcinomas: a reproducibility study. Cytopathology 2011; 23:242-9. [PMID: 21736645 DOI: 10.1111/j.1365-2303.2011.00889.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
OBJECTIVE In recent years, therapeutic approaches including cytoreductive surgery followed by intraperitoneal chemotherapy have proven effective in peritoneal carcinomatosis of colorectal origin. If cytology is to be used to include patients in aggressive treatment regimens, it is necessary to evaluate its performance, particularly in terms of specificity. The aim of this study was to assess interobserver agreement for the detection of intraperitoneal free cancer cells (IFCCs) in patients with non-gynaecological adenocarcinomas. METHODS Over a 5-year period, 1223 patients were recruited in 19 French surgery departments. Peritoneal samples were examined in 14 dispersed pathology laboratories. Giemsa-stained slides were sent to a control reader blind to the previous diagnosis. Discordant cases, concordant positive results and a random selection of negative concordant cases were reviewed by a panel of seven cytopathologists. The 'final diagnosis' was that of the consensus meetings but took into account locally-processed slides. RESULTS Gathering dubious cases with negative results, a 95.6% concordance was achieved between local readers and the control reader. IFCCs were ascertained by the panel in 85 cases (7.0%). Eight of 873 colorectal cancers cases viewed locally were falsely positive (0.9%). Radiotherapy and neoadjuvant therapy had no impact on the false-positive rate as assessed by final validation by the panel (P > 0.05). Samples initially considered as dubious were reclassified as negative by the panel in 24 of 25 cases (96.0%). CONCLUSIONS The panel consensus allowed reclassification of most dubious/equivocal peritoneal cytology cases, whereas clearcut distinction between benign and malignant cases was correctly achieved in almost all cases.
Collapse
Affiliation(s)
- E Piaton
- Hospices Civils de Lyon, Centre de Pathologie Est, Bron Université Lyon 1, Lyon, France.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
25
|
Stewart CJR, Hillery S, Platell C, Puppa G. Assessment of Serosal Invasion and Criteria for the Classification of Pathological (p) T4 Staging in Colorectal Carcinoma: Confusions, Controversies and Criticisms. Cancers (Basel) 2011; 3:164-81. [PMID: 24212611 PMCID: PMC3756354 DOI: 10.3390/cancers3010164] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2010] [Revised: 12/27/2010] [Accepted: 12/29/2010] [Indexed: 02/06/2023] Open
Abstract
Transmural spread by colorectal carcinoma can result in tumor invasion of the serosal surface and, hence, more likely dissemination within the peritoneal cavity and potentially to additional metastatic sites. The adverse prognostic significance of serosal invasion is widely accepted and its presence may be considered an indication for chemotherapy in patients with node negative disease. However, controversy persists regarding the most appropriate criteria for diagnosis and there are also practical difficulties associated with histological assessment in some cases. Therefore, serosal invasion may be under-diagnosed in a significant proportion of tumors, potentially leading to sub-optimal treatment of high-risk patients. The examination of multiple microscopic sections combined with ancillary studies such as cytology preparations, elastin stains, and immunohistochemistry may prove beneficial in selected problematic cases, but these are not used routinely. The relative prognostic significance of serosal invasion and of direct tumor spread to other organs, both of which are incorporated within the pT4 category of the AJCC/UICC TNM staging system, remains unclear. Further studies are required to demonstrate whether recent adjustments to the TNM staging of pT4 tumors are appropriate.
Collapse
Affiliation(s)
- Colin J. R. Stewart
- Department of Histopathology, SJOG Hospital, Perth, Western Australia; E-Mail:
- Author to whom correspondence should be addressed; E-Mail: ; Tel.: 061 08 93402715; Fax: 061 08 93402636
| | - Simon Hillery
- Department of Histopathology, SJOG Hospital, Perth, Western Australia; E-Mail:
| | - Cameron Platell
- Colorectal Surgery Unit, SJOG Hospital, Perth, Western Australia and University of Western Australia; E-Mail:
| | - Giacomo Puppa
- Division of Pathology, ‘G. Fracastoro’ City Hospital, Verona, Italy; E-Mail:
| |
Collapse
|
|
26
|
Perry BC, Wang S, Basson MD. Extracellular pressure stimulates adhesion of sarcoma cells via activation of focal adhesion kinase and Akt. Am J Surg 2010; 200:610-4. [PMID: 21056138 PMCID: PMC3837573 DOI: 10.1016/j.amjsurg.2010.07.013] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2010] [Revised: 07/07/2010] [Accepted: 07/07/2010] [Indexed: 11/19/2022]
Abstract
BACKGROUND The effect of extracellular pressure on adhesion and adhesiogenic focal adhesion kinase (FAK) and Akt signaling in sarcomas was investigated. METHODS Human sarcoma cells (HT-1080 fibrosarcoma, KHOS-240S osteosarcoma, and A-673 rhabdomyosarcoma) were subjected to increased pressure followed by adhesion assay. Two cell lines were pretreated with the FAK inhibitor 1,2,4,5-benzenetetraamine tetrahydrochloride (Y15) or Akt IV inhibitor, followed by Western analysis for activated FAK and Akt. Parallel studies were conducted in cells from a resected human fibrous histiosarcoma. RESULTS Pressure increased adhesion in all 3 sarcoma lines and primary histosarcoma cells by 7% to 18% (n = 6; P < .01 each). Pressure activated FAK and Akt (n = 5; P < .01). Inhibiting FAK or Akt inhibited FAK or Akt phosphorylation and the stimulation of adhesion by increased pressure (n = 5 each; P < .01 each). CONCLUSIONS Pressure increases sarcoma cell adhesiveness via Akt and FAK. Perioperative manipulation or forces in lymphatic or circulatory systems may potentiate local recurrence or distant metastasis.
Collapse
Affiliation(s)
- Brandon C Perry
- Department of Surgery, Michigan State University, Lansing, 48912, USA
| | | | | |
Collapse
|
|
27
|
Noura S, Ohue M, Shingai T, Kano S, Ohigashi H, Yano M, Ishikawa O, Takenaka A, Murata K, Kameyama M. Effects of intraperitoneal chemotherapy with mitomycin C on the prevention of peritoneal recurrence in colorectal cancer patients with positive peritoneal lavage cytology findings. Ann Surg Oncol 2010; 18:396-404. [PMID: 20839059 DOI: 10.1245/s10434-010-1319-2] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2010] [Indexed: 01/15/2023]
Abstract
BACKGROUND The detection of intraperitoneal free cancer cells in colorectal cancer (CRC) patients is associated with a poorer prognosis. The aim of this study was to investigate the effects of intraperitoneal chemotherapy (IPC) with mitomycin C (MMC) on preventing peritoneal recurrence in CRC patients with positive peritoneal lavage cytology findings. METHODS A total of 52 CRC patients who had no clinically confirmed peritoneal dissemination and whose status of peritoneal lavage cytology was positive were investigated. Conventional peritoneal lavage cytology was performed. Overall, 31 of the 52 patients (59.6%) were administered IPC with MMC. Before closure of the abdomen, 4 silicon catheters were inserted into peritoneal cavity. After closure, the perfusate (diluting 20 mg MMC with 500 ml saline) was instilled from the catheter, and all catheters were clumped. All catheters were opened 1 h later. RESULTS The mean follow-up period was 83.1 months. According to univariate analyses of all 52 patients and the subgroup of 36 patients with stage II or III tumors, patients with IPC had a significantly better peritoneal recurrence-free survival and cancer-specific survival than patients who did not receive IPC (P < 0.005). In multivariate analysis, IPC remained an independent prognostic factor for peritoneal recurrence-free survival in all patients. CONCLUSIONS It appears that IPC with MMC is an effective treatment to prevent peritoneal recurrence and prolong the cancer-specific survival in CRC patients without peritoneal dissemination, but who have positive peritoneal lavage cytology. It is necessary to verify the effectiveness of IPC with MMC in a prospective trial.
Collapse
Affiliation(s)
- Shingo Noura
- Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
28
|
Prognostic value of peritoneal cytology and the combination of peritoneal cytology and peritoneal dissemination in colorectal cancer. Dis Colon Rectum 2009; 52:2016-21. [PMID: 19934924 DOI: 10.1007/dcr.0b013e3181b4c46e] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE The value of positive peritoneal cytology in colorectal cancer has been controversial. In this study, we aimed to clarify the prognostic significance of peritoneal cytology and the impact of the combination of peritoneal dissemination and peritoneal cytology on the prognostic evaluation of colorectal cancer. METHODS From January 1997 to December 2005, intraoperative peritoneal cytology was performed on 410 patients who had at least serosal invasion. RESULTS Thirty-one patients (7.6%) had positive peritoneal cytology. Patients with negative cytology showed a significantly better survival rate at five years than those with positive cytology (negative cytology, 68.0%; positive cytology, 20.6%; P < 0.0001). Multivariate analysis revealed that peritoneal cytology is one of the significant prognostic factors. Sixty percent of patients with positive cytology and 30.4% of patients with negative cytology recurred (P = 0.08). Regarding the recurrence site, patients with positive cytology showed a significantly higher recurrence rate of peritoneal dissemination than those with negative cytology (P = 0.0038). Some patients with positive cytology but without evident peritoneal dissemination achieved long-term survival. Additionally, some patients with macroscopic peritoneal dissemination and negative peritoneal cytology also achieved long-term survival. But for those patients with both positive cytology and evident macroscopic peritoneal dissemination, the five-year survival rate was zero. CONCLUSIONS Patients with negative peritoneal cytology had a significantly better five-year survival rate than those with positive peritoneal cytology. In some cases in which either peritoneal cytology or peritoneal dissemination was negative, long-term survival could be achieved.
Collapse
|
|
29
|
Katoh H, Yamashita K, Sato T, Ozawa H, Nakamura T, Watanabe M. Prognostic significance of peritoneal tumour cells identified at surgery for colorectal cancer. Br J Surg 2009; 96:769-77. [PMID: 19526618 DOI: 10.1002/bjs.6622] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND The prognostic significance of intraperitoneal tumour cells (IPCs) in colorectal cancer is not clear. This study aimed to determine whether detection of IPCs could be used a prognostic marker for selecting patients at high risk of recurrence. METHODS The study included 226 patients with colorectal cancer who underwent elective resection. Clinical variables, including the presence of IPCs, were analysed for their prognostic significance. RESULTS Thirty-three patients (14.6 per cent) were positive for IPCs. Univariable analysis indicated that the presence of IPCs was a significant prognostic factor in patients with stage III colorectal cancer; the 5-year disease-specific survival rate was 14 per cent in IPC-positive patients versus 79 per cent in those without IPCs (P < 0.001). Multivariable analysis showed that IPC positivity was the most robust prognostic factor in stage III disease (hazard ratio 2.2; P = 0.003), whereas nodal category (N1 or N2) showed no significant association with prognosis. In addition, IPCs were associated with haematogenous recurrence (P = 0.004) rather than peritoneal or local recurrence (P = 0.077) in patients with stage III disease. CONCLUSION The presence of IPCs is a significant prognostic factor in patients with stage III colorectal cancer.
Collapse
Affiliation(s)
- H Katoh
- Department of Surgery, Kitasato University Hospital, Kitasato 1-15-1, Sagamihara 228-8555, Kanagawa, Japan
| | | | | | | | | | | |
Collapse
|
|
30
|
Long-term prognostic value of conventional peritoneal lavage cytology in patients undergoing curative colorectal cancer resection. Dis Colon Rectum 2009; 52:1312-20. [PMID: 19571710 DOI: 10.1007/dcr.0b013e3181a745a4] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE Free malignant cells in the peritoneal cavity might play a role in the metastasis process. However, this phenomenon needs further elucidation. The aims of this study were to investigate the frequency of free cancer cells detected on cytologic examination of lavage fluid after peritoneal washing in patients undergoing curative surgery for colorectal cancer, to explore risk factors for exfoliation of cancer cells into the peritoneal cavity, and to evaluate the influence peritoneal lavage cytology as a prognostic tool. METHODS Peritoneal lavage was performed in 697 patients undergoing curative resection of colorectal cancer. Before the manipulation of the tumor, 100 mL of physiologic saline solution was administered into the abdominal cavity and the fluid was collected for cytologic examination. Specimens were classified as positive if at least one cancer cell was detected. RESULTS The mean follow-up period was 90.5 months. Overall, 15 (2.2%) of the 697 patients had positive results. Four characteristics were identified as risk factors for exfoliation of cancer cells into the peritoneal cavity: 1) depth of invasion, 2) regional lymph nodes, 3) lymphatic invasion, and 4) venous invasion. In univariate analyses of all 697 patients and the subgroup of 374 patients with pT3 or T4 tumors, patients with positive cytology findings had significantly worse disease-free and cancer-specific survival than patients with negative cytology findings (P < 0.001). On multivariate analysis, peritoneal cytology remained an independent predictor of cancer-specific survival in all patients and in patients with pT3 or pT4 tumors. Only peritoneal cytology was a significant prognostic factor for peritoneal recurrence (P < 0.0001). CONCLUSION Conventional peritoneal cytology is a useful prognostic tool in patients undergoing curative surgery for colorectal cancer and may be helpful in making decisions whether to select intraperitoneal or systemic chemotherapy.
Collapse
|
|
31
|
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.
Collapse
Affiliation(s)
- Wim P Ceelen
- Department of Surgical Oncology, Ghent University Hospital, Ghent, Belgium
| | | |
Collapse
|
|
32
|
Tez M. Can intraoperative intraperitoneal free cancer cell detection techniques identify patients at higher recurrence risk following curative colorectal cancer resection? A meta-analysis. Ann Surg Oncol 2008; 15:2062. [PMID: 18340491 DOI: 10.1245/s10434-008-9853-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2008] [Accepted: 01/25/2008] [Indexed: 11/18/2022]
|
|
33
|
Basson MD. An intracellular signal pathway that regulates cancer cell adhesion in response to extracellular forces. Cancer Res 2008; 68:2-4. [PMID: 18172287 DOI: 10.1158/0008-5472.can-07-2992] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Increasing evidence suggests that tumor cells can regulate their own adhesion via intracellular signals that modulate integrin binding affinity. Although the full pathway has not yet been elucidated, the effects of pressure seem likely to require cytoskeletal mechanosensing, Src, phosphatidylinositol 3-kinase, focal adhesion kinase, and Akt-1 activation. Ultimately, activated focal adhesion kinase accumulates at the membrane in association with beta(1)-integrin heterodimers and may modulate integrin binding affinity. This pathway may be a promising target for manipulation to inhibit metastatic cancer cell adhesion.
Collapse
Affiliation(s)
- Marc D Basson
- Surgical Service, John D. Dingell VA Medical Center and Department of Surgery, Wayne State University, Detroit, Michigan 48201-1932, USA.
| |
Collapse
|
|
34
|
Rekhraj S, Aziz O, Prabhudesai S, Zacharakis E, Mohr F, Athanasiou T, Darzi A, Ziprin P. Can intra-operative intraperitoneal free cancer cell detection techniques identify patients at higher recurrence risk following curative colorectal cancer resection: a meta-analysis. Ann Surg Oncol 2007; 15:60-8. [PMID: 17909914 DOI: 10.1245/s10434-007-9591-5] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2007] [Revised: 08/06/2007] [Accepted: 08/06/2007] [Indexed: 12/17/2022]
Abstract
BACKGROUND Accurate staging of colorectal cancer is important for predicting prognosis and guiding treatment. This study uses meta-analysis to investigate if the pre- or post-resection detection of intraperitoneal free cancer cells can predict recurrence in patients undergoing curative colorectal cancer surgery. METHODS A literature search was performed on all studies between January 1990 and July 2007 comparing the detection of intraperitoneal free cancer cells either pre- or post-resection with prognosis in colorectal cancer. The following prognostic outcomes were meta-analyzed: overall recurrence rate and local recurrence rate. A random-effect model was used and heterogeneity was assessed. RESULTS Nine studies reporting on a total of 1182 subjects matched the selection criteria. Free cancer cells were detected prior to tumor resection in 125/822 (15.2%) of patients and following resection in 64/533 (12%) of patients. Preresection, the absence of tumor cells was associated with a lower overall recurrence (25.2%) compared to the presence of tumor cells [46.4%, odds ratio (OR) = 0.41, confidence interval (CI) 0.19-0.88]; as well as a significantly lower local recurrence (12.2% versus 21.1%, OR = 0.42, CI 0.21-0.82). Postresection, the absence of tumor cells also resulted in significantly lower overall recurrence (17.3%) when compared to the presence of tumor cells (52.6%, OR = 0.07, CI 0.03-0.18). CONCLUSIONS The detection of intraperitoneal free cancer cells is associated with higher recurrence and poorer prognosis. Use of these techniques can identify patients at higher recurrence risk. This could be particularly valuable in stage II disease to identify patients who may benefit from adjuvant chemotherapy.
Collapse
Affiliation(s)
- Sushil Rekhraj
- Department of Biosurgery and Surgical Technology, Imperial College London, St Mary's Hospital, London, W2 1NY, United Kingdom.
| | | | | | | | | | | | | | | |
Collapse
|
|
35
|
Conway WC, Van der Voort van Zyp J, Thamilselvan V, Walsh MF, Crowe DL, Basson MD. Paxillin modulates squamous cancer cell adhesion and is important in pressure-augmented adhesion. J Cell Biochem 2006; 98:1507-1516. [PMID: 16552730 DOI: 10.1002/jcb.20819] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Paxillin is an adapter protein regulating signaling and focal adhesion assembly that has been linked to malignant potential in many malignancies. Overexpression of paxillin has been noted in aggressive tumors. Integrin-mediated binding through the focal adhesion complex is important in metastatic adhesion and is upregulated by extracellular pressure in malignant colonocytes through FAK and Src activation. Neither head and neck cancers nor paxillin have been studied in this regard. We hypothesized that paxillin would play a role in modulating squamous cancer adhesion both at baseline and under conditions of increased extracellular pressure. Using SCC25 tongue squamous cancer cells stably transfected with either an empty selection vector or paxillin expression and selection vectors, we studied adhesion to collagen, paxillin, FAK, and Src expression and phosphorylation in cells maintained for 30 min under ambient or 15 mmHg increased pressure conditions. Paxillin-overexpressing cells exhibited adhesion 121 +/- 2.9% of that observed in vector-only cells (n = 6, P < 0.001) under ambient pressure. Paxillin-overexpression reduced FAK phosphorylation. Pressure stimulated adhesion to 118 +/- 2.3% (n = 6, P < 0.001) of baseline in vector-only cells, similar to its effect in the parental line, and induced paxillin, FAK, and Src phosphorylation. However, increased pressure did not stimulate adhesion or phosphorylate paxillin, FAK, or Src further in paxillin-overexpressing cells. Metastasizing squamous cancer cell adhesiveness may be increased by paxillin-overexpression or by paxillin activation by extracellular pressure during surgical manipulation or growth within a constraining compartment. Targeting paxillin in patients with malignancy and minimal tumor manipulation during surgical resection may be important therapeutic adjuncts.
Collapse
Affiliation(s)
- William C Conway
- Department of Surgery, John D. Dingell VA Medical Center and Wayne State University, Detroit, Michigan 48201-1932, USA
| | | | | | | | | | | |
Collapse
|
|
36
|
Kanellos I, Zacharakis E, Kanellos D, Pramateftakis MG, Betsis D. Prognostic significance of CEA levels and positive cytology in peritoneal washings in patients with colorectal cancer. Colorectal Dis 2006; 8:436-40. [PMID: 16684089 DOI: 10.1111/j.1463-1318.2006.00991.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE The aims of this prospective study were to determine carcinoembryonic antigen (CEA) levels and incidence of cytology in peritoneal washings of patients with colorectal cancer, correlate the results with various histopathological factors and determine their significance as prognostic factors of the disease. METHODS From 1992 to 1999, 98 patients with adenocarcinoma of the colon or intraperitoneal rectum underwent curative surgery and enrolled in this study. RESULTS Overall, 25 (26.3%) of 95 patients were found to have positive cytology. The proportion of patients with positive cytology was higher in the recurrence group (36.4%) than in the groups of 5-year survival and hepatic metastases (24.6% and 26.3%, respectively), but this difference was not significant. The 5-year survival group had the lowest peritoneal CEA levels compared with the other groups, but this difference was not significant. Peritoneal cytology and CEA level alone were not sensitive, specific or accurate enough indicators in predicting survival, hepatic metastases or local recurrence. The analysis of patients with positive cytology and high peritoneal CEA level revealed that their combination can predict local recurrence with accuracy of 85%. CONCLUSIONS The presence of free malignant cells, as detected by cytology and CEA level, in the peritoneal cavity of patients with resectable colorectal cancer had no detectable impact on survival, hepatic metastases or local recurrence rate. However, local recurrence can be predicted with accuracy of 85% in patients who have positive cytology and high peritoneal CEA level at the same time.
Collapse
Affiliation(s)
- I Kanellos
- Fourth Surgical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece.
| | | | | | | | | |
Collapse
|
|
37
|
Lloyd JM, McIver CM, Stephenson SA, Hewett PJ, Rieger N, Hardingham JE. Identification of early-stage colorectal cancer patients at risk of relapse post-resection by immunobead reverse transcription-PCR analysis of peritoneal lavage fluid for malignant cells. Clin Cancer Res 2006; 12:417-23. [PMID: 16428481 DOI: 10.1158/1078-0432.ccr-05-1473] [Citation(s) in RCA: 96] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
PURPOSE Colorectal cancer patients diagnosed with stage I or II disease are not routinely offered adjuvant chemotherapy following resection of the primary tumor. However, up to 10% of stage I and 30% of stage II patients relapse within 5 years of surgery from recurrent or metastatic disease. The aim of this study was to determine if tumor-associated markers could detect disseminated malignant cells and so identify a subgroup of patients with early-stage colorectal cancer that were at risk of relapse. EXPERIMENTAL DESIGN We recruited consecutive patients undergoing curative resection for early-stage colorectal cancer. Immunobead reverse transcription-PCR of five tumor-associated markers (carcinoembryonic antigen, laminin gamma2, ephrin B4, matrilysin, and cytokeratin 20) was used to detect the presence of colon tumor cells in peripheral blood and within the peritoneal cavity of colon cancer patients perioperatively. Clinicopathologic variables were tested for their effect on survival outcomes in univariate analyses using the Kaplan-Meier method. A multivariate Cox proportional hazards regression analysis was done to determine whether detection of tumor cells was an independent prognostic marker for disease relapse. RESULTS Overall, 41 of 125 (32.8%) early-stage patients were positive for disseminated tumor cells. Patients who were marker positive for disseminated cells in post-resection lavage samples showed a significantly poorer prognosis (hazard ratio, 6.2; 95% confidence interval, 1.9-19.6; P = 0.002), and this was independent of other risk factors. CONCLUSION The markers used in this study identified a subgroup of early-stage patients at increased risk of relapse post-resection for primary colorectal cancer. This method may be considered as a new diagnostic tool to improve the staging and management of colorectal cancer.
Collapse
Affiliation(s)
- Julia M Lloyd
- Department of Haematology-Oncology, Hetzel Institute, The Queen Elizabeth Hospital, 28 Woodville Road, Woodville, SA 5011, Australia
| | | | | | | | | | | |
Collapse
|