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Takamizawa Y, Tsukamoto S, Kato T, Nagata H, Moritani K, Kanemitsu Y. Short- and long-term outcomes of robotic and laparoscopic surgery in rectal cancer: a propensity score-matched analysis. Surg Endosc 2025; 39:184-193. [PMID: 39485536 DOI: 10.1007/s00464-024-11374-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Accepted: 10/19/2024] [Indexed: 11/03/2024]
Abstract
PURPOSE The relative benefits of robotic surgery and laparoscopic surgery are controversial in rectal cancer. This study compared the short- and long-term outcomes of robotic surgery with those of laparoscopic surgery in patients with rectal cancer using propensity score analysis. METHODS This study analyzed consecutive patients who underwent minimally invasive surgery for stage I-III rectal cancer between April 2014 and October 2020. After propensity score matching (PSM), short-term outcomes, relapse-free survival, and overall survival were compared between the robotic surgery (RS) group and the laparoscopic surgery (LS) group. RESULTS During the study period, 251 patients underwent laparoscopic surgery and 193 underwent robotic surgery. PSM resulted in 160 matched pairs (After PSM, the percentages of patients with stage I, II, and III disease were respectively 56%, 19%, and 24% in the LS group and 49%, 23%, and 28% in the RS group (P = 0.462). Median operation time was 239 min in the LS group and 284 min in the RS group (P = 0.001). The C-reactive protein level on postoperative day 3 was significantly lower in the RS group (4.63 mg/mL vs. 5.86 mg/mL, P = 0.013). Postoperative complications, including ileus and Clavien-Dindo grade II or higher complications, were 6% vs. 1% (P = 0.006) and 21% vs. 12% (P = 0.024) in the LS and RS groups, respectively. The 5-year relapse-free survival rate was 88.5% in the LS group and 90.5% in the RS group (P = 0.525); the respective 5-year overall survival rates were 97.3 and 93.8% (P = 0.283). The 5-year cumulative local and distant recurrence rates were 3.3% vs. 3.3% (P = 0.665) and 9.7% vs. 7.7% (P = 0.464) in the LS and RS groups, respectively CONCLUSION: Robotic surgery can be a feasible treatment modality for rectal cancer, with lower frequencies of postoperative ileus and Clavien-Dindo grade II or higher complications than laparoscopic surgery and no difference in long-term outcomes.
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Affiliation(s)
- Yasuyuki Takamizawa
- Department of Colorectal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
| | - Shunsuke Tsukamoto
- Department of Colorectal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Takeharu Kato
- Department of Colorectal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Hiroshi Nagata
- Department of Colorectal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Konosuke Moritani
- Department of Colorectal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Yukihide Kanemitsu
- Department of Colorectal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
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Gerdin A, Park J, Häggström J, Segelman J, Matthiessen P, Lydrup ML, Rutegård M. Anastomotic leakage after resection for rectal cancer and recurrence-free survival in relation to postoperative C-reactive protein levels. Int J Colorectal Dis 2024; 39:193. [PMID: 39621059 PMCID: PMC11611975 DOI: 10.1007/s00384-024-04766-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/17/2024] [Indexed: 12/06/2024]
Abstract
BACKGROUND Anastomotic leakage after rectal cancer surgery is linked to reduced survival and higher recurrence rates. While an aggravated inflammatory response may worsen outcomes, few studies have explored the combined effects of leakage and inflammation. METHODS This is a retrospective multicenter cohort study including patients operated with anterior resection for rectal cancer in Sweden during 2014-2018. Anastomotic leakage within 12 months was exposure and primary outcome was recurrence-free survival. Mediation analysis was performed to evaluate the potential effect of systemic inflammatory response, as measured by the highest postoperative C-reactive protein (CRP) level within 14 days of surgery. Confounders were chosen using a causal diagram. RESULTS Some 1036 patients were eligible for analysis, of whom 218 (21%) experienced an anastomotic leakage. At the end of follow-up at a median of 61 months after surgery, recurrence-free survival amounted to 82.6% and 77.8% in the group with and without leakage, respectively. The median highest postoperative CRP value after surgery was higher in the leakage group (219 mg/l), compared with the group without leakage (108 mg/l). Leakage did not lead to worse recurrence-free survival (HR 0.66; 95% CI 0.43-0.94), and there was no apparent effect through postoperative highest CRP (HR 1.12; 95% CI 0.93-1.29). CONCLUSIONS In conclusion, anastomotic leakage, with its accompanying CRP increase, was not found to be associated with recurrence-free survival after anterior resection for rectal cancer in this patient cohort. Larger, even more detailed studies are needed to further investigate this topic.
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Affiliation(s)
- Anders Gerdin
- Department of Diagnostics and Intervention, Surgery, Umeå University, 901 85, Umeå, Sweden.
| | - Jennifer Park
- Department of Surgery, Sahlgrenska University Hospital, SSORG - Scandinavian Surgical Outcomes Research Group, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Jenny Häggström
- Department of Statistics, Umeå School of Business, Economics and Statistics, Umeå University, Umeå, Sweden
| | - Josefin Segelman
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Sweden
- Department of Surgery, Ersta Hospital, Stockholm, Sweden
| | - Peter Matthiessen
- Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Marie-Louise Lydrup
- Department of Surgery, Skåne University Hospital, Malmö, Lund University, Lund, Sweden
| | - Martin Rutegård
- Department of Diagnostics and Intervention, Surgery, Umeå University, 901 85, Umeå, Sweden
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Dong ZK, Wang YF, Li WP, Jin WL. Neurobiology of cancer: Adrenergic signaling and drug repurposing. Pharmacol Ther 2024; 264:108750. [PMID: 39527999 DOI: 10.1016/j.pharmthera.2024.108750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 10/04/2024] [Accepted: 11/05/2024] [Indexed: 11/16/2024]
Abstract
Cancer neuroscience, as an emerging converging discipline, provides us with new perspectives on the interactions between the nervous system and cancer progression. As the sympathetic nervous system, in particular adrenergic signaling, plays an important role in the regulation of tumor activity at every hierarchical level of life, from the tumor cell to the tumor microenvironment, and to the tumor macroenvironment, it is highly desirable to dissect its effects. Considering the far-reaching implications of drug repurposing for antitumor drug development, such a large number of adrenergic receptor antagonists on the market has great potential as one of the means of antitumor therapy, either as primary or adjuvant therapy. Therefore, this review aims to summarize the impact of adrenergic signaling on cancer development and to assess the status and prospects of intervening in adrenergic signaling as a therapeutic tool against tumors.
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Affiliation(s)
- Zi-Kai Dong
- The First Clinical Medical College of Lanzhou University, Lanzhou 730000, PR China; Institute of Cancer Neuroscience, Medical Frontier Innovation Research Center, The First Hospital of Lanzhou University, The First Clinical Medical College of Lanzhou University, Lanzhou 730000, PR China
| | - Yong-Fei Wang
- The First Clinical Medical College of Lanzhou University, Lanzhou 730000, PR China; Institute of Cancer Neuroscience, Medical Frontier Innovation Research Center, The First Hospital of Lanzhou University, The First Clinical Medical College of Lanzhou University, Lanzhou 730000, PR China
| | - Wei-Ping Li
- The First Clinical Medical College of Lanzhou University, Lanzhou 730000, PR China; Department of Urology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, PR China
| | - Wei-Lin Jin
- The First Clinical Medical College of Lanzhou University, Lanzhou 730000, PR China; Institute of Cancer Neuroscience, Medical Frontier Innovation Research Center, The First Hospital of Lanzhou University, The First Clinical Medical College of Lanzhou University, Lanzhou 730000, PR China.
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Houqiong J, Yuli Y, Fujia G, Gengmei G, Yaxiong L, Yahang L, Tao L, Yang L, Dongning L, Taiyuan L. Body image and quality of life undergoing totally robotic versus robotic-assisted distal gastrectomy: a retrospective propensity score matched cohort study. BMC Surg 2024; 24:295. [PMID: 39385219 PMCID: PMC11463158 DOI: 10.1186/s12893-024-02597-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Accepted: 09/27/2024] [Indexed: 10/12/2024] Open
Abstract
BACKGROUND With the improvement of anastomotic techniques and the iteration of anastomotic instruments, robotic intracorporeal suturing has become increasingly proficient. The era of fully intracorporeal anastomosis in robotic gastric cancer resection is emerging. This study aims to explore the impact of totally robotic distal gastrectomy (TRDG) and robotic-assisted distal gastrectomy (RADG) on patients' quality of life. PATIENTS AND METHODS This study is a comparative retrospective study of propensity score matching. This study included 306 patients who underwent robotic distal gastrectomy for gastric cancer between June 2016 and December 2023 at our center. Covariates used in the propensity score included sex, age, BMI, ASA score, maximum tumour diameter, degree of histological differentiation, Pathological TNM stage, Pathological T stage, Pathological N stage, and Lauren classification. Outcome measures included operative time, intraoperative bleeding, time to first venting, time to first fluid intake, postoperative hospital stay, total hospitalization cost, total length of abdominal incision, postoperative complications, inflammatory response, body image, and quality of life. RESULTS According to the results of the study, compared with the RADG group, the TRDG group had a faster recovery time for gastrointestinal function (P = 0.025), shorter length of abdominal incision (P < 0.001), fewer days in the hospital (P = 0.006) less pain (P < 0.001), less need for additional analgesia (P = 0.013), and a postoperative white blood cell count (P < 0.001) and C-reactive protein content indexes were lower (P<0.001). In addition, the TRDG group had significantly better body imagery and cosmetic scores (P = 0.015), physical function (P = 0.039), role function (P = 0.046), and global function (P = 0.021) than the RARS group. Meanwhile, the TRDG group had milder symptoms of fatigue (P = 0.037) and pain (P < 0.001). The PASQ Total Subscale Score (P < 0.001) and Global Subscale Score (P < 0.001) were significantly lower in the TRDG group than in the RADG group at postoperative 3 months. CONCLUSION Totally robotic distal gastrectomy has a smaller incision, faster gastrointestinal recovery time, fewer days of postoperative hospitalization, and lower inflammatory markers than robotic-assisted distal gastrectomy. At the same time, postoperative cosmetic and quality of life outcomes were satisfactory. Clinically, these benefits translate to enhanced patient recovery, reduced surgical trauma, and better postoperative outcomes. These findings could guide surgeons in selecting more effective surgical approaches for patients undergoing gastrectomy, leading to better overall patient satisfaction and outcomes.
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Affiliation(s)
- Ju Houqiong
- Department of General surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China
- Gastrointestinal Surgical Institute, Nanchang University, Nanchang, Jiangxi, 330006, China
| | - Yuan Yuli
- Department of General surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China
- Gastrointestinal Surgical Institute, Nanchang University, Nanchang, Jiangxi, 330006, China
| | - Guo Fujia
- Department of Pathology, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China
| | - Gao Gengmei
- Department of General surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China
- Gastrointestinal Surgical Institute, Nanchang University, Nanchang, Jiangxi, 330006, China
| | - Liu Yaxiong
- Department of General surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China
- Gastrointestinal Surgical Institute, Nanchang University, Nanchang, Jiangxi, 330006, China
| | - Liang Yahang
- Department of General surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China
- Gastrointestinal Surgical Institute, Nanchang University, Nanchang, Jiangxi, 330006, China
| | - Li Tao
- Department of General surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China
- Gastrointestinal Surgical Institute, Nanchang University, Nanchang, Jiangxi, 330006, China
| | - Liu Yang
- Department of General surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China
- Gastrointestinal Surgical Institute, Nanchang University, Nanchang, Jiangxi, 330006, China
| | - Liu Dongning
- Department of General surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China.
- Gastrointestinal Surgical Institute, Nanchang University, Nanchang, Jiangxi, 330006, China.
| | - Li Taiyuan
- Department of General surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China.
- Gastrointestinal Surgical Institute, Nanchang University, Nanchang, Jiangxi, 330006, China.
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Mokhtari L, Hosseinzadeh F, Nourazarian A. Biochemical implications of robotic surgery: a new frontier in the operating room. J Robot Surg 2024; 18:91. [PMID: 38401027 DOI: 10.1007/s11701-024-01861-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 02/01/2024] [Indexed: 02/26/2024]
Abstract
Robotic surgery represents a milestone in surgical procedures, offering advantages such as less invasive methods, elimination of tremors, scaled motion, and 3D visualization. This in-depth analysis explores the complex biochemical effects of robotic methods. The use of pneumoperitoneum and steep Trendelenburg positioning can decrease pulmonary compliance and splanchnic perfusion while increasing hypercarbia. However, robotic surgery reduces surgical stress and inflammation by minimizing tissue trauma. This contributes to faster recovery but may limit immune function. Robotic procedures also limit ischemia-reperfusion injury and oxidative damage compared to open surgery. They also help preserve native antioxidant defenses and coagulation. In a clinical setting, robotic procedures reduce blood loss, pain, complications, and length of stay compared to traditional procedures. However, risks remain, including device failure, the need for conversion to open surgery and increased costs. On the oncology side, there is still debate about margins, recurrence, and long-term survival. The advent of advanced technologies, such as intraoperative biosensors, localized drug delivery systems, and the incorporation of artificial intelligence, may further improve the efficiency of robotic surgery. However, ethical dilemmas regarding patient consent, privacy, access, and regulation of this disruptive innovation need to be addressed. Overall, this review sheds light on the complex biochemical implications of robotic surgery and highlights areas that require additional mechanistic investigation. It presents a comprehensive approach to responsibly maximize the potential of robotic surgery to improve patient outcomes, integrating technical skill with careful consideration of physiological and ethical issues.
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Affiliation(s)
- Leila Mokhtari
- Department of Nursing, Khoy University of Medical Sciences, Khoy, Iran
| | | | - Alireza Nourazarian
- Department of Basic Medical Sciences, Khoy University of Medical Sciences, Khoy, Iran.
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Jiang Y, Gao S, Sun H, Wu X, Gu J, Wu H, Liao Y, Ben-Ami R, Miao C, Shen R, Liu J, Chen W. Targeting NEDD8 suppresses surgical stress-facilitated metastasis of colon cancer via restraining regulatory T cells. Cell Death Dis 2024; 15:8. [PMID: 38177106 PMCID: PMC10767093 DOI: 10.1038/s41419-023-06396-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 12/10/2023] [Accepted: 12/15/2023] [Indexed: 01/06/2024]
Abstract
Regulatory T cells (Tregs) are a key determinant for the immunosuppressive and premetastatic niche for cancer progression after surgery resection. However, the precise mechanisms regulating Tregs function during surgical stress-facilitated cancer metastasis remain unknown. This study aims to unravel the mechanisms and explore potential strategies for preventing surgical stress-induced metastasis by targeting NEDD8. Using a surgical stress mouse model, we found that surgical stress results in the increased expression of NEDD8 in Tregs. NEDD8 depletion abrogates postoperative lung metastasis of colon cancer cells by inhibiting Treg immunosuppression and thereby partially recovering CD8+T cell and NK cell-mediated anti-tumor immunity. Furthermore, Treg mitophagy and mitochondrial respiration exacerbated in surgically stressed mice were attenuated by NEDD8 depletion. Our observations suggest that cancer progression may result from surgery-induced enhancement of NEDD8 expression and the subsequent immunosuppressive function of Tregs. More importantly, depleting or inhibiting NEDD8 can be an efficient strategy to reduce cancer metastasis after surgery resection by regulating the function of Tregs.
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Affiliation(s)
- Yi Jiang
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Shanghai Key laboratory of Perioperative Stress and Protection, Shanghai, 200032, China
| | - Shenjia Gao
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Shanghai Key laboratory of Perioperative Stress and Protection, Shanghai, 200032, China
| | - Hao Sun
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Shanghai Key laboratory of Perioperative Stress and Protection, Shanghai, 200032, China
| | - Xinyi Wu
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Shanghai Key laboratory of Perioperative Stress and Protection, Shanghai, 200032, China
| | - Jiahui Gu
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Shanghai Key laboratory of Perioperative Stress and Protection, Shanghai, 200032, China
| | - Han Wu
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Shanghai Key laboratory of Perioperative Stress and Protection, Shanghai, 200032, China
| | - Yun Liao
- School of Basic Medical Science, Shanghai Medical College of Fudan University, Shanghai, 200032, China
| | - Ronen Ben-Ami
- Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv, 6997801, Israel
| | - Changhong Miao
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Shanghai Key laboratory of Perioperative Stress and Protection, Shanghai, 200032, China
| | - Rong Shen
- Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
| | - Jinlong Liu
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China.
| | - Wankun Chen
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
- Shanghai Key laboratory of Perioperative Stress and Protection, Shanghai, 200032, China.
- Department of Anesthesiology, Shanghai Geriatric Medical Center, Shanghai, 201104, China.
- Department of Anesthesiology, QingPu Branch of Zhongshan Hospital, Fudan University, Shanghai, 201799, China.
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Ye SP, Lu WJ, Liu DN, Yu HX, Wu C, Xu HC, Li TY. Comparison of short-term efficacy analysis of medium-rectal cancer surgery with robotic natural orifice specimen extraction and robotic transabdominal specimen extraction. BMC Surg 2023; 23:336. [PMID: 37940918 PMCID: PMC10634172 DOI: 10.1186/s12893-023-02216-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Accepted: 10/04/2023] [Indexed: 11/10/2023] Open
Abstract
BACKGROUND With the development of minimally invasive technology, the trauma caused by surgery get smaller, At the same time, the specimen extraction surgery through the natural orifice is more favored by experts domestically and abroad, robotic surgery has further promoted the development of specimen extraction surgery through the natural orifice. The aim of current study is to compare the short-term outcomes of robotic-assisted natural orifice specimen extraction (NOSES ) and transabdominal specimen extraction(TRSE ) in median rectal cancer surgery. METHODS From January 2020 to January 2023, 87 patients who underwent the NOSES or TRSE at the First Affiliated Hospital of Nanchang University were included in the study, 4 patients were excluded due to liver metastasis. Of these, 50 patients were in the TRSE and 33 patients in the NOSES. Short-term efficacy was compared in the two groups. RESULTS The NOSES group had less operation time (P < 0.001), faster recovery of gastrointestinal function (P < 0.001), shorter abdominal incisions (P < 0.001), lower pain scores(P < 0.001). lower Inflammatory indicators of the white blood cell count and C-reactive protein content at 1, 3, and 5 days after surgery (P < 0.001, P = 0.037). There were 9 complications in the NOSES group and 11 complications in the TRSE group(P = 0.583). However, there were no wound complications in the NOSES group. The number of postoperative hospital stays seems to be same in the two groups. And there was no significant difference in postoperative anus function (P = 0.591). CONCLUSIONS This study shows that NOSES and TRSE can achieve similar radical treatment effects, NOSES is a feasible and safe way to take specimens for rectal cancer surgery in accordance with the indication for NOSES.
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Affiliation(s)
- Shan-Ping Ye
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi Province, China
| | - Wei-Jie Lu
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi Province, China
| | - Dong-Ning Liu
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi Province, China
| | - Hong-Xin Yu
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi Province, China
| | - Can Wu
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi Province, China
| | - Hao-Cheng Xu
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi Province, China
| | - Tai-Yuan Li
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi Province, China.
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Xiao L, Li X, Fang C, Yu J, Chen T. Neurotransmitters: promising immune modulators in the tumor microenvironment. Front Immunol 2023; 14:1118637. [PMID: 37215113 PMCID: PMC10196476 DOI: 10.3389/fimmu.2023.1118637] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 04/12/2023] [Indexed: 05/24/2023] Open
Abstract
The tumor microenvironment (TME) is modified by its cellular or acellular components throughout the whole period of tumor development. The dynamic modulation can reprogram tumor initiation, growth, invasion, metastasis, and response to therapies. Hence, the focus of cancer research and intervention has gradually shifted to TME components and their interactions. Accumulated evidence indicates neural and immune factors play a distinct role in modulating TME synergistically. Among the complicated interactions, neurotransmitters, the traditional neural regulators, mediate some crucial regulatory functions. Nevertheless, knowledge of the exact mechanisms is still scarce. Meanwhile, therapies targeting the TME remain unsatisfactory. It holds a great prospect to reveal the molecular mechanism by which the interplay between the nervous and immune systems regulate cancer progression for laying a vivid landscape of tumor development and improving clinical treatment.
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Affiliation(s)
- Luxi Xiao
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Xunjun Li
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Chuanfa Fang
- Department of Gastrointestinal and Hernia Surgery, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, Ganzhou, Jiangxi, China
| | - Jiang Yu
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Tao Chen
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
- Department of Gastrointestinal and Hernia Surgery, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, Ganzhou, Jiangxi, China
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Hebert JD, Neal JW, Winslow MM. Dissecting metastasis using preclinical models and methods. Nat Rev Cancer 2023; 23:391-407. [PMID: 37138029 DOI: 10.1038/s41568-023-00568-4] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/27/2023] [Indexed: 05/05/2023]
Abstract
Metastasis has long been understood to lead to the overwhelming majority of cancer-related deaths. However, our understanding of the metastatic process, and thus our ability to prevent or eliminate metastases, remains frustratingly limited. This is largely due to the complexity of metastasis, which is a multistep process that likely differs across cancer types and is greatly influenced by many aspects of the in vivo microenvironment. In this Review, we discuss the key variables to consider when designing assays to study metastasis: which source of metastatic cancer cells to use and where to introduce them into mice to address different questions of metastasis biology. We also examine methods that are being used to interrogate specific steps of the metastatic cascade in mouse models, as well as emerging techniques that may shed new light on previously inscrutable aspects of metastasis. Finally, we explore approaches for developing and using anti-metastatic therapies, and how mouse models can be used to test them.
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Affiliation(s)
- Jess D Hebert
- Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA
| | - Joel W Neal
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
- Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA
| | - Monte M Winslow
- Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
- Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
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10
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Cox PBW, Pisters TPRM, de Korte-de Boer D, Pennings CH, Melenhorst J, Buhre WFFA. Thoracic epidural analgesia vs. patient-controlled intravenous analgesia for patients undergoing open or laparoscopic colorectal cancer surgery: An observational study. EUROPEAN JOURNAL OF ANAESTHESIOLOGY AND INTENSIVE CARE 2023; 2:e0013. [PMID: 39916756 PMCID: PMC11783615 DOI: 10.1097/ea9.0000000000000013] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
Abstract
BACKGROUND Thoracic epidural analgesia (TEA) is an invasive technique with potential side effects but is widely used in enhanced recovery after surgery (ERAS) programmes in colorectal cancer surgery. The effects of TEA on postoperative length of hospital stay (LOS) or morbidity is still debated. OBJECTIVES The main objective was to evaluate the postoperative analgesic effectiveness of TEA compared with patient-controlled intravenous analgesia (PCIA) after open or laparoscopic colorectal surgery, and whether TEA contributes to enhanced recovery. DESIGN A retrospective single-centre, observational study. SETTING Dutch tertiary-care university hospital. PATIENTS All consecutive adult patients undergoing colorectal cancer surgery from 1 January 2014 to 31 December 2016, with ASA status I-IV, were included. Exclusion criteria were hypersensitivity to opioid or local anaesthetic substances, or the use of multiple secondary anaesthetic techniques. MAIN OUTCOME MEASURES The primary outcome, postoperative pain assessed with a Numeric Rating Scale on postoperative days 1 to 3 inclusive. Secondary endpoints were LOS, the incidence of epidural related side effects, major complications and the 5-year survival rate. Using linear mixed models, pain scores were compared between patients who received TEA and PCIA. RESULTS Of 422 enrolled patients, 110 (32%) received TEA and 234 (68%) PCIA. Patients in the TEA group had lower pain scores: estimated NRS difference at rest; -0.79; 95% CI, -1.1 to -0.49; P < 0.001 and during movement -1.06; 95% CI, -1.39 to -0.73; P < 0.001. LOS, 30-day complication rate and overall survival at 5 years did not differ between the groups. CONCLUSIONS TEA in open or laparoscopic colorectal surgery is associated with moderately better postoperative pain control but does not affect LOS, postoperative morbidity, mortality nor long-term survival. The current clinical indication for TEA in colorectal surgery remains unchanged. TRIAL REGISTRATION International clinical trial registration number: ISRCTN11426678; retrospectively registered 26 February 2021.
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Affiliation(s)
- P Boris W Cox
- From the Department of Anaesthesiology and Pain Medicine (PBWC, TPRMP, D deK deB, CHP, WFFAB), and the Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands (JM)
| | - Tom P R M Pisters
- From the Department of Anaesthesiology and Pain Medicine (PBWC, TPRMP, D deK deB, CHP, WFFAB), and the Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands (JM)
| | - Dianne de Korte-de Boer
- From the Department of Anaesthesiology and Pain Medicine (PBWC, TPRMP, D deK deB, CHP, WFFAB), and the Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands (JM)
| | - Christoph H Pennings
- From the Department of Anaesthesiology and Pain Medicine (PBWC, TPRMP, D deK deB, CHP, WFFAB), and the Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands (JM)
| | - Jarno Melenhorst
- From the Department of Anaesthesiology and Pain Medicine (PBWC, TPRMP, D deK deB, CHP, WFFAB), and the Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands (JM)
| | - Wolfgang F F A Buhre
- From the Department of Anaesthesiology and Pain Medicine (PBWC, TPRMP, D deK deB, CHP, WFFAB), and the Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands (JM)
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11
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Tumor immunology. Clin Immunol 2023. [DOI: 10.1016/b978-0-12-818006-8.00003-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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12
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Houqiong J, Ziwen W, Chonghan Z, Penghui H, Hongxin Y, Weijie L, Dongning L, Taiyuan L. Comparison of transabdominal wall specimen retrieval and natural orifice specimen extraction robotic surgery in the outcome of colorectal cancer treatment. Front Surg 2023; 10:1092128. [PMID: 36874472 PMCID: PMC9978825 DOI: 10.3389/fsurg.2023.1092128] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 01/16/2023] [Indexed: 02/18/2023] Open
Abstract
Background Natural orifice specimen extraction surgery (NOSES), as a new star of minimally invasive techniques, has been increasingly favored and promoted in the field of surgery around the world. Most previous studies were comparative studies of laparoscopic NOSES and conventional laparoscopic surgery. However, there is little research on comparing robotic colorectal cancer NOSES with conventional robotic-assisted colorectal cancer resection surgery. Participant and methods This study is a retrospective study of propensity score matching (PSM). This study included Ninety-one propensity score-matched pairs of the participant who had undergone robotic colorectal cancer resection surgery at our center between January 2017 and December 2020. The covariates used in the propensity score included gender, age, BMI, ASA score, maximum tumor diameter, the tumor's height from the anal verge, histological differentiation, AJCC stage, T stage, N stage, and history of previous abdominal surgery. The outcome measurement criteria included postoperative complications, inflammatory response, pelvic floor function, anal function, cosmetic outcome, quality of life, disease-free survival (DFS), and overall survival (OS). Results The robotic NOSES group had faster recovery time from gastrointestinal function (P = 0.014), shorter abdominal incision length (P < 0.001), less pain (P < 0.001), less additional analgesia required (P < 0.001), and lower postoperative indicators of white blood cell count (P < 0.001) and C-reactive protein content compared to the robotic-assisted resection surgery (RARS) group (P = 0.035). Additionally, the robotic NOSES group had significantly better body imagery (P < 0.001), cosmetic scores (P < 0.001), somatic function (P = 0.003), role function (P = 0.039), emotional function (P = 0.001), social function (P = 0.004), and overall function (P < 0.001) than the RARS group. The two groups demonstrated no significant difference between DFS and OS. Conclusion Robotic colorectal cancer NOSES is a safe and feasible minimally invasive procedure and offers shorter abdominal incisions, less pain, less surgical stress response, and better postoperative quality of life. Therefore, this technique can be further promoted for colorectal cancer patients eligible for NOSES.
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Affiliation(s)
- Ju Houqiong
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.,Laboratory of Digestive Surgery, Nanchang University, Nanchang, China
| | - Wan Ziwen
- Laboratory of Digestive Surgery, Nanchang University, Nanchang, China.,The First Clinical Medical College of Nanchang University, Nanchang, China
| | - Zhong Chonghan
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.,Laboratory of Digestive Surgery, Nanchang University, Nanchang, China
| | - He Penghui
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.,Laboratory of Digestive Surgery, Nanchang University, Nanchang, China
| | - Yu Hongxin
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.,Laboratory of Digestive Surgery, Nanchang University, Nanchang, China
| | - Lu Weijie
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.,Laboratory of Digestive Surgery, Nanchang University, Nanchang, China
| | - Liu Dongning
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.,Laboratory of Digestive Surgery, Nanchang University, Nanchang, China
| | - Li Taiyuan
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.,Laboratory of Digestive Surgery, Nanchang University, Nanchang, China
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13
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Hung KC, Chang PC, Hsu CW, Lan KM, Liao SW, Lin YT, Huang PW, Sun CK. Usefulness of Analgesia Nociception Index for guiding intraoperative opioid administration: a systematic review and meta-analysis. Minerva Anestesiol 2023; 89:74-84. [PMID: 36282226 DOI: 10.23736/s0375-9393.22.16697-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION This study primarily aimed at investigating the efficacy of Analgesia Nociception Index (ANI) for guiding intraoperative opioid administration in patients receiving surgery under general anesthesia. EVIDENCE ACQUISITION The Medline, Embase, Google scholar, and the Cochrane Library databases were searched from inception to April 2022 for randomized controlled trials. The primary outcome was intraoperative opioid administration, while the secondary outcomes included postoperative opioid consumption, pain score, emergency time, risk of nausea/vomiting (PONV), and Postanesthesia Care Unit (PACU) stay. EVIDENCE SYNTHESIS Six studies including 399 participants (published from 2015 to 2022) focused on non-cardiac surgery, including spine surgery (two trials), breast surgery (two trials), gynecologic surgery (one trial), and laparoscopic cholecystectomy (one trial) were included. Meta-analysis revealed no difference in intraoperative opioid administration with the use of ANI-guided analgesia compared to the control group that used conventional clinical measurements (e.g., heart rate) to guide opioid use [standardized mean difference (SMD)=-0.17, 95% CI: -0.56 to 0.22, P=0.39, I2=72%, six trials, 399 participants]. Gender-based subgroup analysis showed effectiveness of ANI for reducing opioid administration in female patients (SMD=-0.53, P=0.02). There were no differences in postoperative recovery characteristics including pain score [Mean difference (MD): -0.03, P=0.79], opioid consumption (SMD: -0.34, P=0.08), emergence time (MD=1.12, P=0.47), length of stay in the PACU (MD: -0.56, P=0.83), and risk of PONV [risk ratio(RR): 0.75, P=0.46] between the two groups. CONCLUSIONS Analgesia nociception index-guided analgesia was unable to reduce intraoperative opioid administration compared to monitoring using conventional clinical parameters. Further studies are required to support our findings.
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Affiliation(s)
- Kuo-Chuan Hung
- Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Po-Chih Chang
- Division of Thoracic Surgery, Department of Surgery, Kaohsiung Medical University Hospital/Kaohsiung Medical University, Kaohsiung, Taiwan.,Weight Management Center, Kaohsiung Medical University Hospital/Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Sports Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Program in Biomedical Engineering, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chih-Wei Hsu
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kuo-Mao Lan
- Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Shu-Wei Liao
- Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Yao-Tsung Lin
- Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Ping-Wen Huang
- Department of Emergency Medicine, Show Chwan Memorial Hospital, Changhua City, Taiwan
| | - Cheuk-Kwan Sun
- Department of Emergency Medicine, E-Da Hospital, Kaohsiung, Taiwan - .,College of Medicine, I-Shou University, Kaohsiung, Taiwan
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14
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de Boniface J, Szulkin R, Johansson ALV. Major surgical postoperative complications and survival in breast cancer: Swedish population-based register study in 57 152 women. Br J Surg 2022; 109:977-983. [PMID: 35929050 PMCID: PMC10364684 DOI: 10.1093/bjs/znac275] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 05/06/2022] [Accepted: 07/15/2022] [Indexed: 08/02/2023]
Abstract
BACKGROUND Postoperative complications may activate prometastatic systemic pathways through tissue damage, wound healing, infection, and inflammation. Postoperative complications are associated with inferior survival in several types of cancer. The aim was to determine the association between postoperative complications and survival in breast cancer. METHODS This population-based cohort included women operated for T1-3 N0-3 M0 invasive breast cancer in Sweden from 2008 to 2017. Only major surgical postoperative complications leading to readmission and/or reoperation within 30 days were considered. Main outcomes were overall survival (OS) and breast cancer-specific survival (BCSS). Prospectively collected nationwide register data were used. Multivariable Cox models were adjusted for clinical and socioeconomic confounders and co-morbidity. RESULTS Among 57 152 women, major surgical postoperative complications were registered for 1854 patients. Median follow-up was 6.22 (0.09-11.70) years. Overall, 9163 patients died, and 3472 died from breast cancer. Major surgical postoperative complications were more common after mastectomy with or without immediate reconstruction (7.3 and 4.3 per cent respectively) than after breast-conserving surgery (2.3 per cent). Unadjusted 5-year OS and BCSS rates were 82.6 (95 per cent c.i. 80.8 to 84.5) and 92.1 (90.8 to 93.5) per cent respectively for women with a major surgical postoperative complication, and 88.8 (88.6 to 89.1) and 95.0 (94.8 to 95.2) per cent for those without a complication (P < 0.001). After adjustment, all-cause and breast cancer mortality rates remained higher after a major surgical postoperative complication (OS: HR 1.32, 95 per cent c.i. 1.15 to 1.51; BCSS: HR 1.31, 1.04 to 1.65). After stratification for type of breast surgery, this association remained significant only for women who had mastectomy without reconstruction (OS: HR 1.41, 1.20 to 1.66; BCSS: HR 1.36, 1.03 to 1.79). CONCLUSION Major surgical postoperative complications are associated with inferior survival, especially after mastectomy. These results underline the importance of surgical de-escalation.
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Affiliation(s)
- Jana de Boniface
- Correspondence to: Jana de Boniface, Department of Surgery, Breast Centre, Capio St Göran’s Hospital, 11219 Stockholm, Sweden (e-mail: )
| | - Robert Szulkin
- SDS Life Science, Danderyd, Sweden
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Anna L V Johansson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Cancer Registry of Norway, Oslo, Norway
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15
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Ni L, Sun P, Ai M, Kong L, Xu R, Li J. Berberine inhibited the formation of metastasis by intervening the secondary homing of colorectal cancer cells in the blood circulation to the lung and liver through HEY2. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 104:154303. [PMID: 35802997 DOI: 10.1016/j.phymed.2022.154303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 06/17/2022] [Accepted: 06/26/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Metastasis is the leading cause of death in patients with colorectal cancer (CRC). The 5-year survival rate of CRC patients in whom the cancer has spread to distant sites is 13.5%. The most common sites of CRC metastasis are liver and lung. The principal therapies for CRC metastatic disease are surgery, but its benefits are limited. PURPOSE This study aimed to reveal the regulatory mechanism of berberine on secondary homing of CRC cells to form metastatic focus. This was more valuable than the previous direct study of the migration and metastasis characteristics of CRC cells. METHODS In this study, we used the functional enrichment analysis of differentially expressed genes after berberine treatment and investigated co-expression modules related with CRC metastasis by WGCNA. PPI and survival analyses of significant modules were also conducted. The biological functions of berberine in CRC lung and liver metastasis were investigated by a series of in vitro and in vivo experiments: MTT, colony formation and mouse tail vein injection. And we scanned through the entire extracellular domain of HEY2 protein for autodocking analysis with berberine. RESULTS We found the differentially expressed genes (DEGs) after berberine treatment were related with cancer progression and metastasis related pathways. Through WGCNA analysis, four cancer progression and metastasis related modules were detected. After PPI and survival analysis, we identified and validated HEY2 as a hub gene, high expression and poor survival at the metastatic stage. Functionally, berberine inhibited the survival, invasion and migration of CRC cells in vitro and in vivo. Mechanistically, berberine treatment down-regulated the expression of HEY2, metastasis related protein E-cadherin, β-catenin and Cyclin D1 during Mesenchymal epithelial transformation (MET). Berberine and HEY2 showed a significant interaction, and berberine binded to HEY2 protein at the residue HIS-99 interface with a hydrogen-bond distance of 1.9A. CONCLUSIONS We revealed that berberine could significantly inhibit the expression of hub gene HEY2 and metastasis related proteins E-cadherin and β-catenin and Cyclin D1 during MET in CRC lung and liver metastases. In total, HEY2 was a promising candidate biomarker for prognosis and molecular characteristics in CRC metastasis.
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Affiliation(s)
- Lulu Ni
- Department of Basic Medicine, Jiangnan University, Wuxi 214122, PR China
| | - Ping Sun
- Department of Pathology, The Affiliated Wuxi NO. 2 People's Hospital of Nanjing Medical University, Wuxi 214000,PR China
| | - Min Ai
- Laboratory Animal Center of Shanghai Jiao Tong University, Shanghai 200240, PR China
| | - Lingzhong Kong
- Department of Rehabilitation Acupuncture Medicine, Bozhou People's Hospital, Bozhou, Anhui 236800, PR China
| | - Rongrong Xu
- Department of Pathology, The Affiliated Wuxi NO. 2 People's Hospital of Nanjing Medical University, Wuxi 214000,PR China
| | - Jiangan Li
- Department of Emergency, The Affiliated Wuxi NO. 2 People's Hospital of Nanjing Medical University, No. 68 Zhongshan Road, Wuxi 214000, PR China.
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Grahn O, Lundin M, Chapman SJ, Rutegård J, Matthiessen P, Rutegård M. Postoperative nonsteroidal anti-inflammatory drugs in relation to recurrence, survival and anastomotic leakage after surgery for colorectal cancer. Colorectal Dis 2022; 24:933-942. [PMID: 35108455 PMCID: PMC9541253 DOI: 10.1111/codi.16074] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 12/07/2021] [Accepted: 01/21/2022] [Indexed: 12/23/2022]
Abstract
AIM The aim of this work was to investigate whether nonsteroidal anti-inflammatory drugs (NSAIDs) could be beneficial or harmful when used perioperatively for colorectal cancer patients, as inflammation may affect occult disease and anastomotic healing. METHOD This is a protocol-based retrospective cohort study on colorectal cancer patients operated on between 2007 and 2012 at 21 hospitals in Sweden. NSAID exposure was retrieved from postoperative analgesia protocols, while outcomes and patient data were retrieved from the Swedish Colorectal Cancer Registry. Older or severely comorbid patients, as well as those with disseminated or nonradically operated tumours were excluded. Multivariable regression with adjustment for confounders was performed, estimating hazard ratios (HRs) for long-term outcomes and odds ratios (ORs) for short-term outcomes, including 95% confidence intervals (CIs). RESULTS Some 6945 patients remained after exclusion, of whom 3996 were treated at hospitals where a NSAID protocol was in place. No association was seen between NSAIDs and recurrence-free survival (HR 0.97, 95% CI 0.87-1.09). However, a reduction in cancer recurrence was detected (HR 0.83, 95% CI 0.72-0.95), which remained significant when stratifying into locoregional (HR 0.68, 95% CI 0.48-0.97) and distant recurrences (HR 0.85, 95% CI 0.74-0.98). Anastomotic leakage was less frequent (HR 0.69%, 95% CI 0.51-0.94) in the NSAID-exposed, mainly due to a risk reduction in colo-rectal and ileo-rectal anastomoses (HR 0.47, 95% CI 0.33-0.68). CONCLUSION There was no association between NSAID exposure and recurrence-free survival, but an association with reduced cancer recurrence and the rate of anastomotic leakage was detected, which may depend on tumour site and anastomotic location.
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Affiliation(s)
- Oskar Grahn
- Department of Surgical and Perioperative Sciences, SurgeryUmeå UniversityUmeåSweden
| | - Mathias Lundin
- Department of Surgical and Perioperative Sciences, SurgeryUmeå UniversityUmeåSweden
- Department of StatisticsUmeå School of Business and EconomicsUmeå UniversityUmeåSweden
| | - Stephen J. Chapman
- Leeds Institute of Medical Research at St James'sUniversity of LeedsLeedsUK
| | - Jörgen Rutegård
- Department of Surgical and Perioperative Sciences, SurgeryUmeå UniversityUmeåSweden
| | - Peter Matthiessen
- Department of SurgeryFaculty of Medicine and HealthÖrebro UniversityÖrebroSweden
| | - Martin Rutegård
- Department of Surgical and Perioperative Sciences, SurgeryUmeå UniversityUmeåSweden
- Wallenberg Centre for Molecular MedicineUmeå UniversityUmeåSweden
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17
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Application Effect of Robot-Assisted Laparoscopy in Hepatectomy for Colorectal Cancer Patients with Liver Metastases. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:5492943. [PMID: 35756424 PMCID: PMC9225905 DOI: 10.1155/2022/5492943] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 03/28/2022] [Accepted: 04/07/2022] [Indexed: 11/17/2022]
Abstract
Objective Application effect of Leonardo's robot-assisted laparoscopy in hepatectomy for colorectal cancer patients with liver metastases. Methods A total of 122 patients with sCRLM treated in our hospital from May 2015 to June 2018 were selected and divided into observation group (n = 61) and control group (n = 61) according to random number table method. The observation group was treated with robot-assisted laparoscopic hepatectomy, while the control group was treated with conventional laparoscopic hepatectomy. The perioperative time, intraoperative blood transfusion, intraoperative blood loss, average intraoperative blood transfusion, and hepatic portal occlusion time of the two groups were observed. Serum cortisol (Cor), norepinephrine (NE), and glucose (Glu) levels were detected before and after surgery in the two groups. The oxygen consumption and carbon dioxide output of patients were measured 1 day before surgery and 1~3 days after surgery, and the resting energy expenditure (REE) value was calculated. The levels of CD3+, CD4+, and CD8+ were determined by flow cytometry. The incidence of complications was compared between the two groups. Patients were followed up for 3 years after discharge, and Kaplan-Meier method was used to analyze the survival of the two groups. Results The operation time, intraoperative blood transfusion, intraoperative blood loss, and average intraoperative blood transfusion in the observation group were all less than those in the control group, and the differences were statistically significant (P < 0.05). Three days after operation, the levels of serum Cor, NE, and Glu were increased in both groups, and the observation group was lower than the control group; the difference was statistically significant (P < 0.05). The REE level of observation group was lower than that of control group after 1 day, 2 days, and 3 days after surgery, and the difference was statistically significant (P < 0.05). Three days after operation, the levels of serum CD3+ and CD4+ were decreased in both groups, and the observation group was higher than the control group; the difference was statistically significant (P < 0.05). The incidence of complications in the observation group (3.28%) was lower than that in the control group (13.11%); the difference was statistically significant (P < 0.05).There was no significant difference in survival rate between the two groups after 1, 2, and 3 years of follow-up (P > 0.05). Conclusion The application of robot-assisted laparoscopy in patients with sCRLM can effectively improve the perioperative situation of patients, reduce stress, energy metabolism, and immune damage, and reduce the incidence of complications.
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Zhao P, Shen Y, Li M, Dan H, Zhao Z, Zhang J. Integration of Transcriptomics and Metabolomics Reveals the Antitumor Mechanism Underlying Tadalafil in Colorectal Cancer. Front Pharmacol 2022; 13:793499. [PMID: 35694253 PMCID: PMC9184725 DOI: 10.3389/fphar.2022.793499] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 04/21/2022] [Indexed: 11/25/2022] Open
Abstract
The potential role of tadalafil, a PDE5 inhibitor, in anticancer activity and prolonged survival has been proposed. However, the systematic effects of tadalafil in colorectal cancer were not fully understood. In this study, we assessed the anti-tumor activity of tadalafil in human colorectal cancer cells. A systematic perspective of the tadalafil-induced anti-tumor mechanism was provided by the integration of transcriptomics and metabolomics. We found that differentially expressed genes (DEGs) were mainly involved in microRNAs in cancer, purine metabolism, glycosphingolipid biosynthesis, arginine biosynthesis, and amino acid metabolism. Amino acid metabolism, especially alanine, aspartate, and glutamate metabolism was the most of the differentially accumulated metabolites (DAMs) through the analysis of metabolomics. The conjoint analysis of DEGs and DAMs presented that they were also mainly involved in alanine, aspartate, and glutamate metabolism. Amino acid metabolism-related genes, GPT, GGT5, and TAT, were significantly decreased after tadalafil treatment. In particular, the disturbance of alanine, aspartate, and glutamate metabolism may be the explanation for the major mechanism resulting from tadalafil anti-tumor activity.
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Affiliation(s)
- Pan Zhao
- The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi’an, China
| | - Yao Shen
- The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi’an, China
| | - Mengyang Li
- The Faculty of Hepatopancreatobiliary Surgery, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing, China
| | - Hanjun Dan
- The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi’an, China
| | - Zhiming Zhao
- The Faculty of Hepatopancreatobiliary Surgery, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing, China
- *Correspondence: Zhiming Zhao, ; Jian Zhang,
| | - Jian Zhang
- The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi’an, China
- *Correspondence: Zhiming Zhao, ; Jian Zhang,
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Gray K, Avitsian R, Kakumanu S, Venkatraghavan L, Chowdhury T. The Effects of Anesthetics on Glioma Progression: A Narrative Review. J Neurosurg Anesthesiol 2022; 34:168-175. [PMID: 32658099 DOI: 10.1097/ana.0000000000000718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 06/15/2020] [Indexed: 11/26/2022]
Abstract
There are many established factors that influence glioma progression, including patient age, grade of tumor, genetic mutations, extent of surgical resection, and chemoradiotherapy. Although the exposure time to anesthetics during glioma resection surgery is relatively brief, the hemodynamic changes involved and medications used, as well as the stress response throughout the perioperative period, may also influence postoperative outcomes in glioma patients. There are numerous studies that have demonstrated that choice of anesthesia influences non-brain cancer outcomes; of particular interest are those describing that the use of total intravenous anesthesia may yield superior outcomes compared with volatile agents in in vitro and human studies. Much remains to be discovered on the topic of anesthesia's effect on glioma progression.
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Affiliation(s)
| | - Rafi Avitsian
- Department of General Anesthesiology, Cleveland Clinic, Cleveland, OH
| | - Saranya Kakumanu
- Department of Radiation Oncology, Cancer Care Manitoba, Winnipeg, MB
| | - Lashmi Venkatraghavan
- Department of Anesthesia and Pain Medicine, Toronto Western Hospital, Toronto, ON, Canada
| | - Tumul Chowdhury
- Department of Anesthesiology, Perioperative, and Pain Medicine, Health Sciences Center, University of Manitoba
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Lv G, Zhao D, Li G, Qi M, Dong X, Li P. When Experiencing a Surgery: Gastrointestinal Cancer Patients’ Longitudinal Trajectories in Psychological Stress and Their Association with Quality of Recovery. Asia Pac J Oncol Nurs 2022; 9:100064. [PMID: 35615664 PMCID: PMC9125671 DOI: 10.1016/j.apjon.2022.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 04/05/2022] [Indexed: 11/16/2022] Open
Abstract
Objective Surgical treatment, particularly for gastrointestinal cancer, is a burdensome prospect for many patients. Psychological stress is a common complaint; however, little is known about its patterns in perioperative patients. This study aimed to identify distinct trajectories of perioperative stress and explore antecedent factors and hospitalization outcomes among different trajectories in patients with gastrointestinal cancer. Methods A longitudinal study was conducted on 203 patients with gastrointestinal surgical cancer at a specialized oncology hospital in China. Psychological stress was assessed at five perioperative time points (1–3 days before surgery; 1–3 days, 4–6 days, 7–9 days after surgery, and before discharge). A growth mixture model was used to analyze the potential stress trajectories. Multinomial logistic regression was used to identify the characteristics associated with different trajectories. Results Three stress trajectories were identified: recovery class (RC, 60.6%), chronic class (CC, 29.5%), and deterioration class (DC, 9.9%). Compared with CC, RC exhibited a shorter length of stay and better recovery quality, and was related to employment, low illness perception, and positive coping; DC reported lower recovery quality from 7 to 9 days after surgery to discharge and was associated with poor education level, history of surgery, stoma, smoking, and preoperative insomnia. Conclusions Most surgical patients were insulated from stress due to psychosocial resources, and thus displayed good recovery. However, many patients had moderate stress that did not improve or worsen over the perioperative period, which still needs to be screened and provided with early stress management.
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Santander Ballestín S, Lanuza Bardaji A, Marco Continente C, Luesma Bartolomé MJ. Antitumor Anesthetic Strategy in the Perioperatory Period of the Oncological Patient: A Review. Front Med (Lausanne) 2022; 9:799355. [PMID: 35252243 PMCID: PMC8894666 DOI: 10.3389/fmed.2022.799355] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 01/11/2022] [Indexed: 12/13/2022] Open
Abstract
The stress response triggered by the surgical aggression and the transient immunosuppression produced by anesthetic agents stimulate the inadvertent dispersion of neoplastic cells and, paradoxically, tumor progression during the perioperative period. Anesthetic agents and techniques, in relation to metastatic development, are investigated for their impact on long-term survival. Scientific evidence indicates that inhaled anesthetics and opioids benefit immunosuppression, cell proliferation, and angiogenesis, providing the ideal microenvironment for tumor progression. The likely benefit of reducing their use, or even replacing them as much as possible with anesthetic techniques that protect patients from the metastatic process, is still being investigated. The possibility of using "immunoprotective" or "antitumor" anesthetic techniques would represent a turning point in clinical practice. Through understanding of pharmacological mechanisms of anesthetics and their effects on tumor cells, new perioperative approaches emerge with the aim of halting and controlling metastatic development. Epidural anesthesia and propofol have been shown to maintain immune activity and reduce catecholaminergic and inflammatory responses, considering the protective techniques against tumor spread. The current data generate hypotheses about the influence of anesthesia on metastatic development, although prospective trials that determinate causality are necessary to make changes in clinical practice.
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Affiliation(s)
- Sonia Santander Ballestín
- Department of Pharmacology, Physiology and Legal and Forensic Medicine, Faculty of Medicine, University of Zaragoza, Zaragoza, Spain
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22
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Shembrey C, Smith J, Grandin M, Williams N, Cho HJ, Mølck C, Behrenbruch C, Thomson BNJ, Heriot AG, Merino D, Hollande F. Longitudinal Monitoring of Intra-Tumoural Heterogeneity Using Optical Barcoding of Patient-Derived Colorectal Tumour Models. Cancers (Basel) 2022; 14:581. [PMID: 35158849 PMCID: PMC8833441 DOI: 10.3390/cancers14030581] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 01/16/2022] [Accepted: 01/19/2022] [Indexed: 02/01/2023] Open
Abstract
Geno- and phenotypic heterogeneity amongst cancer cell subpopulations are established drivers of treatment resistance and tumour recurrence. However, due to the technical difficulty associated with studying such intra-tumoural heterogeneity, this phenomenon is seldom interrogated in conventional cell culture models. Here, we employ a fluorescent lineage technique termed "optical barcoding" (OBC) to perform simultaneous longitudinal tracking of spatio-temporal fate in 64 patient-derived colorectal cancer subclones. To do so, patient-derived cancer cell lines and organoids were labelled with discrete combinations of reporter constructs, stably integrated into the genome and thus passed on from the founder cell to all its clonal descendants. This strategy enables the longitudinal monitoring of individual cell lineages based upon their unique optical barcodes. By designing a novel panel of six fluorescent proteins, the maximum theoretical subpopulation resolution of 64 discriminable subpopulations was achieved, greatly improving throughput compared with previous studies. We demonstrate that all subpopulations can be purified from complex clonal mixtures via flow cytometry, permitting the downstream isolation and analysis of any lineages of interest. Moreover, we outline an optimized imaging protocol that can be used to image optical barcodes in real-time, allowing for clonal dynamics to be resolved in live cells. In contrast with the limited intra-tumour heterogeneity observed in conventional 2D cell lines, the OBC technique was successfully used to quantify dynamic clonal expansions and contractions in 3D patient-derived organoids, which were previously demonstrated to better recapitulate the heterogeneity of their parental tumour material. In summary, we present OBC as a user-friendly, inexpensive, and high-throughput technique for monitoring intra-tumoural heterogeneity in in vitro cell culture models.
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Affiliation(s)
- Carolyn Shembrey
- Department of Clinical Pathology, University of Melbourne, Melbourne, VIC 3000, Australia; (C.S.); (J.S.); (M.G.); (N.W.); (C.M.); (C.B.)
- Victorian Comprehensive Cancer Centre, University of Melbourne Centre for Cancer Research, Melbourne, VIC 3000, Australia
| | - Jai Smith
- Department of Clinical Pathology, University of Melbourne, Melbourne, VIC 3000, Australia; (C.S.); (J.S.); (M.G.); (N.W.); (C.M.); (C.B.)
- Victorian Comprehensive Cancer Centre, University of Melbourne Centre for Cancer Research, Melbourne, VIC 3000, Australia
| | - Mélodie Grandin
- Department of Clinical Pathology, University of Melbourne, Melbourne, VIC 3000, Australia; (C.S.); (J.S.); (M.G.); (N.W.); (C.M.); (C.B.)
- Victorian Comprehensive Cancer Centre, University of Melbourne Centre for Cancer Research, Melbourne, VIC 3000, Australia
| | - Nathalia Williams
- Department of Clinical Pathology, University of Melbourne, Melbourne, VIC 3000, Australia; (C.S.); (J.S.); (M.G.); (N.W.); (C.M.); (C.B.)
- Victorian Comprehensive Cancer Centre, University of Melbourne Centre for Cancer Research, Melbourne, VIC 3000, Australia
| | - Hyun-Jung Cho
- Biological Optical Microscopy Platform, University of Melbourne, Melbourne, VIC 3010, Australia;
| | - Christina Mølck
- Department of Clinical Pathology, University of Melbourne, Melbourne, VIC 3000, Australia; (C.S.); (J.S.); (M.G.); (N.W.); (C.M.); (C.B.)
- Victorian Comprehensive Cancer Centre, University of Melbourne Centre for Cancer Research, Melbourne, VIC 3000, Australia
| | - Corina Behrenbruch
- Department of Clinical Pathology, University of Melbourne, Melbourne, VIC 3000, Australia; (C.S.); (J.S.); (M.G.); (N.W.); (C.M.); (C.B.)
- Victorian Comprehensive Cancer Centre, University of Melbourne Centre for Cancer Research, Melbourne, VIC 3000, Australia
- The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC 3010, Australia;
- Department of General Surgical Specialties, The Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC 3050, Australia;
| | - Benjamin NJ. Thomson
- Department of General Surgical Specialties, The Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC 3050, Australia;
- Department of Surgery, the Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC 3050, Australia
| | - Alexander G. Heriot
- The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC 3010, Australia;
- Department of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia
- Department of Surgery, St Vincent’s Hospital, Melbourne, VIC 3065, Australia
| | - Delphine Merino
- Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia;
- School of Cancer Medicine, La Trobe University, Melbourne, VIC 3086, Australia
- Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia
- Department of Medical Biology, The Faculty of Medicine, Dentistry and Health Science, University of Melbourne, Melbourne, VIC 3010, Australia
| | - Frédéric Hollande
- Department of Clinical Pathology, University of Melbourne, Melbourne, VIC 3000, Australia; (C.S.); (J.S.); (M.G.); (N.W.); (C.M.); (C.B.)
- Victorian Comprehensive Cancer Centre, University of Melbourne Centre for Cancer Research, Melbourne, VIC 3000, Australia
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Epidermal Growth Factor Receptor as Target for Perioperative Elimination of Circulating Colorectal Cancer Cells. JOURNAL OF ONCOLOGY 2022; 2022:3577928. [PMID: 35035479 PMCID: PMC8759909 DOI: 10.1155/2022/3577928] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 12/17/2021] [Indexed: 12/15/2022]
Abstract
Surgical resection of the tumor is the primary treatment of colorectal cancer patients. However, we previously demonstrated that abdominal surgery promotes the adherence of circulating tumor cells (CTC) in the liver and subsequent liver metastasis development. Importantly, preoperative treatment with specific tumor-targeting monoclonal antibodies (mAb) prevented surgery-induced liver metastasis development in rats. This study investigated whether the epidermal growth factor receptor (EGFR) represents a suitable target for preoperative antibody treatment of colorectal cancer patients undergoing surgery. The majority of patients with resectable colorectal liver metastases were shown to have EGFR + CTCs. Three different anti-EGFR mAbs (cetuximab, zalutumumab, and panitumumab) were equally efficient in the opsonization of tumor cell lines. Additionally, all three mAbs induced antibody-dependent cellular phagocytosis (ADCP) of tumor cells by macrophages at low antibody concentrations in vitro, independent of mutations in EGFR signaling pathways. The plasma of cetuximab-treated patients efficiently opsonized tumor cells ex vivo and induced phagocytosis. Furthermore, neither proliferation nor migration of epithelial cells was affected in vitro, supporting that wound healing will not be hampered by treatment with low anti-EGFR mAb concentrations. These data support the use of a low dose of anti-EGFR mAbs prior to resection of the tumor to eliminate CTCs without interfering with the healing of the anastomosis. Ultimately, this may reduce the risk of metastasis development, consequently improving long-term patient outcome significantly.
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Moorthy A, Eochagáin AN, Buggy DJ. Can Acute Postoperative Pain Management After Tumour Resection Surgery Modulate Risk of Later Recurrence or Metastasis? Front Oncol 2022; 11:802592. [PMID: 34976840 PMCID: PMC8716859 DOI: 10.3389/fonc.2021.802592] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 11/30/2021] [Indexed: 12/13/2022] Open
Abstract
Background Cancer is a leading cause of mortality worldwide, but death is rarely from the primary tumour: Rather it is multi-organ dysfunction from metastatic disease that is responsible for up to 90% of cancer-related deaths. Surgical resection of the primary tumour is indicated in 70% of cases. The perioperative stress response, tissue hypoxia at the site of surgery, and acute pain contribute to immunosuppression and neo-angiogenesis, potentially promoting tumour survival, proliferation, and metastasis. Poorly controlled acute postoperative pain decreases Natural Killer (NK) immune cell activity, which could potentially facilitate circulating tumour cells from evading immune detection. This consequently promotes tumour growth and distal metastasis. Methods We conducted a comprehensive literature search for links between acute pain and cancer outcomes using multiple online databases. Relevant articles from January 1st, 2010 to September 1st, 2021 were analysed and appraised on whether postoperative pain control can modulate the risk of recurrence, metastasis, and overall cancer survival. Results Although experimental and retrospective clinical data suggest a plausible role for regional anaesthesia in cancer outcome modulation, this has not been supported by the single, largest prospective trial to date concerning breast cancer. While there are mixed results on anaesthesiology drug-related interventions, the most plausible data relates to total intravenous anaesthesia with propofol, and to systemic administration of lidocaine. Conclusion The hypothesis that anaesthetic and analgesic technique during cancer surgery could influence risk of subsequent recurrence or metastasis has been prevalent for >15 years. The first, large-scale definitive trial among women with breast cancer found robust equivalent findings between volatile anaesthesia with opioid analgesia and regional anaesthesia. Therefore, while regional anaesthesia during tumour resection does not seem to have any effect on cancer outcomes, it remains plausible that other anaesthetic techniques (e.g. total intravenous anaesthesia and systemic lidocaine infusion) might influence oncologic outcome in other major tumour resection surgery (e.g. colorectal and lung). Therefore, another large trial is needed to definitively answer these specific research questions. Until such evidence is available, perioperative analgesia for cancer surgery of curative intent should be based on patient co-morbidity and non-cancer endpoints, such as optimising analgesia and minimising postoperative complications.
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Affiliation(s)
- Aneurin Moorthy
- Anaesthesiology & Perioperative Medicine Research Fellow, Division of Anaesthesiology and Peri-operative Medicine, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Aisling Ní Eochagáin
- Anaesthesiology Research Fellow, St. James's University Hospital, Dublin, Ireland
| | - Donal J Buggy
- Consultant and Professor, Division of Anaesthesiology and Peri-operative Medicine, Mater Misericordiae University Hospital, School of Medicine, University College, Dublin, Ireland.,Outcomes Research, Cleveland Clinic, Cleveland, OH, United States
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25
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Liu HM, Ma LL, Li C, Cao B, Jiang Y, Han L, Xu R, Lin J, Zhang D. The molecular mechanism of chronic stress affecting the occurrence and development of breast cancer and potential drug therapy. Transl Oncol 2021; 15:101281. [PMID: 34875482 PMCID: PMC8652015 DOI: 10.1016/j.tranon.2021.101281] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Accepted: 11/08/2021] [Indexed: 12/14/2022] Open
Abstract
According to the 2020 data released by the International Agency for Research on Cancer, breast cancer has surpassed lung cancer as the world's most newly diagnosed first-time cancer. Compared with patients with other types of cancer, those with breast cancer experience greater mental stress and more severe psychological impacts because of the life-threatening diagnosis, physical changes, treatment side effects, and family and social life dysfunctions. These usually manifest as anxiety, depression, nervousness, and insomnia, all of which elicit stress responses. Particularly under chronic stress, the continuous release of neurotransmitters from the neuroendocrine system can have a highly profound impact on the occurrence and prognosis of breast cancer. However, because of the complex mechanisms underlying chronic stress and the variability in individual tolerance, evidence of the role of chronic stress in the occurrence and evolution of breast cancer remains unclear. This article reviewed previous research on the correlation between chronic stress and the occurrence and development of breast cancer, particularly the molecular mechanism through which chronic stress promotes breast cancer via neurotransmitters secreted by the nervous system. We also review the progress in the development of potential drugs or blockers for the treatment of breast cancer by targeting the neuroendocrine system.
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Affiliation(s)
- Hui-Min Liu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, No. 1066 Avenue Liutai, Chengdu 611137, China
| | - Le-le Ma
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, No. 1066 Avenue Liutai, Chengdu 611137, China
| | - Chunyu Li
- National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Bo Cao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, No. 1066 Avenue Liutai, Chengdu 611137, China; National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yifang Jiang
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Road Shierqiao, Chengdu 610072, China
| | - Li Han
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, No. 1066 Avenue Liutai, Chengdu 611137, China
| | - Runchun Xu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, No. 1066 Avenue Liutai, Chengdu 611137, China.
| | - Junzhi Lin
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Road Shierqiao, Chengdu 610072, China.
| | - Dingkun Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, No. 1066 Avenue Liutai, Chengdu 611137, China.
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Lilley R, Chan E, Ng N, Orr A, Szostok M, Yeh GTT, Tulloch R, Ramsay G, Mokini Z, Forget P. Recurrence Kinetics after Laparoscopic Versus Open Surgery in Colon Cancer. A Meta-Analysis. J Clin Med 2021; 10:jcm10184163. [PMID: 34575272 PMCID: PMC8466495 DOI: 10.3390/jcm10184163] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 09/03/2021] [Accepted: 09/10/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is a leading cause of mortality worldwide and in the UK. Surgical resection is the main curative treatment modality available and using a laparoscopic vs. an open approach may have a direct influence on the inflammatory response, influencing cancer biology and potentially the recurrence kinetics by promoting cancer growth. METHODS This systematic review aims to compare laparoscopic with open surgery for the treatment of colon cancer with a specific focus on the moment of the recurrence. We included randomised controlled trials in intended curative surgery for colon cancer in adults. INTERVENTIONS Studies investigating laparoscopic vs. open resection as an intended curative treatment for patients with confirmed carcinoma of the colon. The two co-primary outcomes were the time to recurrence and the overall survival (OS) and disease-free survival (DFS) at three and five years. Meta-analyses were done on the mean differences. RESULTS After selection, we reviewed ten randomised controlled trials. Most of the trials did not display a statistically significant difference in either DFS or OS at three or at five years when comparing laparoscopic to open surgery. Groups did not differ for the OS and DFS, especially regarding the time needed to observe the median recurrence rate. The quality of evidence (GRADE) was moderate to very low. CONCLUSION We observed no difference in the recurrence kinetics, OS or DFS at three or five years when comparing laparoscopic to open surgery in colon cancer.
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Affiliation(s)
- Ross Lilley
- Institute of Applied Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK; (R.L.); (E.C.); (N.N.); (A.O.); (M.S.); (G.T.T.Y.); (R.T.)
| | - Evangeline Chan
- Institute of Applied Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK; (R.L.); (E.C.); (N.N.); (A.O.); (M.S.); (G.T.T.Y.); (R.T.)
| | - Nicklaus Ng
- Institute of Applied Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK; (R.L.); (E.C.); (N.N.); (A.O.); (M.S.); (G.T.T.Y.); (R.T.)
| | - Amber Orr
- Institute of Applied Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK; (R.L.); (E.C.); (N.N.); (A.O.); (M.S.); (G.T.T.Y.); (R.T.)
| | - Marcin Szostok
- Institute of Applied Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK; (R.L.); (E.C.); (N.N.); (A.O.); (M.S.); (G.T.T.Y.); (R.T.)
| | - Gloria Ting Ting Yeh
- Institute of Applied Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK; (R.L.); (E.C.); (N.N.); (A.O.); (M.S.); (G.T.T.Y.); (R.T.)
| | - Ross Tulloch
- Institute of Applied Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK; (R.L.); (E.C.); (N.N.); (A.O.); (M.S.); (G.T.T.Y.); (R.T.)
| | - George Ramsay
- Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen AB25 2ZD, UK;
- Department of General Surgery, NHS Grampian, Aberdeen AB25 2ZN, UK
| | - Zhirajr Mokini
- Independent Researcher, supported by the European Society of Anaesthesiology and Intensive Care Mentorship Programme, B-1000 Brussels, Belgium;
| | - Patrice Forget
- Epidemiology Group, Institute of Applied Health Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK
- Department of Anaesthesia, NHS Grampian, Aberdeen AB25 2ZN, UK
- Correspondence:
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Conversion to Open Surgery in Laparoscopic Colorectal Cancer Resection: Predictive Factors and its Impact on Long-Term Outcomes. A Case Series Study. SURGICAL LAPAROSCOPY, ENDOSCOPY & PERCUTANEOUS TECHNIQUES 2021; 32:28-34. [PMID: 34369479 DOI: 10.1097/sle.0000000000000986] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 06/18/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Laparoscopic resection is the treatment of choice for colorectal cancer. Rates of conversion to open surgery range between 7% and 30% and controversy exists as to the effect of this on oncologic outcomes. The objective of this study was to analyze what factors are predictive of conversion and what effect they have on oncologic outcomes. METHODS From a prospective database of patients undergoing laparoscopic surgery between 2000 and 2018 a univariate and multivariate analyses were made of demographic, pathologic, and surgical variables together with complementary treatments comparing purely laparoscopic resection with conversions to open surgery. Overall and disease-free survival were compared using the Kaplan-Meier method. RESULTS Of a total of 829 patients, 43 (5.18%) converted to open surgery. In the univariate analysis, 12 variables were significantly associated with conversion, of which left-sided resection [odds ratio (OR): 2.908; P=0.02], resection of the rectum (OR: 4.749, P=0.014), and local invasion of the tumor (OR: 6.905, P<0.01) were independently predictive factors in the multiple logistic regression. Female sex was associated with fewer conversions (OR: 0.375, P=0.012). The incidence and pattern of relapses were similar in both groups and there were no significant differences between overall and disease-free survival. CONCLUSIONS Left-sided resections, resections of the rectum and tumor invasion of neighboring structures are associated with higher rates of conversion. Female sex is associated with fewer conversions. Conversion to open surgery does not compromise oncologic outcomes at 5 and 10 years.
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Meguro S, Haga N, Imai H, Yoshida Y, Takinami-Honda R, Matsuoka K, Hoshi S, Hata J, Sato Y, Akaihata H, Kataoka M, Ogawa S, Kojima Y. Association Between Surgical Stress and Biochemical Recurrence After Robotic Radical Prostatectomy. JSLS 2021; 25:JSLS.2020.00078. [PMID: 33879996 PMCID: PMC8035824 DOI: 10.4293/jsls.2020.00078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Background and Objectives This study was conducted to identify whether surgical stress during the peri-operative period of robot-assisted radical prostatectomy might affect biochemical recurrence in patients with positive surgical margins. Methods Participants in the present study were 324 consecutive patients with localized prostate cancer who underwent robot-assisted radical prostatectomy between February 2013 and June 2018. Positive surgical margins were diagnosed in 61 of them. Patients with positive surgical margins were divided into those with (n = 19) and those without (n = 42) biochemical recurrence. Lymph node dissection, estimated blood loss, inhalation anesthetic volume, and surgical duration were evaluated as indicators of surgical stress. White blood cell count, C-reactive protein, body temperature, and usage of analgesics were postoperatively evaluated as surrogate markers of surgical stress. The associations between factors, including patients' characteristics and pathological features, and biochemical recurrence were investigated. Results In univariate analyses, surgical duration (P = 0.004), D'Amico risk class (P = 0.002), Gleason score (P = 0.022) and the number of positive cores in prostate biopsy (P = 0.009) were statistically significantly associated with biochemical recurrence. In multivariate analyses, only surgical duration was significantly associated with biochemical recurrence (P = 0.042), at a cut-off value of surgical duration of 228.5 minutes. Conclusions Prolonged surgical duration is associated with biochemical recurrence in patients with positive surgical margins. Thus, surgical duration should be limited as much as possible to reduce surgical stress, which might cause biochemical recurrence.
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Affiliation(s)
- Satoru Meguro
- Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Nobuhiro Haga
- Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Hitomi Imai
- Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Yuki Yoshida
- Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Ruriko Takinami-Honda
- Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Kanako Matsuoka
- Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Seiji Hoshi
- Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Junya Hata
- Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Yuichi Sato
- Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Hidenori Akaihata
- Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Masao Kataoka
- Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Soichiro Ogawa
- Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Yoshiyuki Kojima
- Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan
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Park SY, Lee SM, Park JS, Kim HJ, Choi GS. Robot Surgery Shows Similar Long-term Oncologic Outcomes as Laparoscopic Surgery for Mid/Lower Rectal Cancer but Is Beneficial to ypT3/4 After Preoperative Chemoradiation. Dis Colon Rectum 2021; 64:812-821. [PMID: 33833141 DOI: 10.1097/dcr.0000000000001978] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND The long-term oncologic efficacy of robotic surgery for patients with rectal cancer is unknown. OBJECTIVE The aim of the study was to investigate survival outcomes of robotic total mesorectal excision for mid/low rectal cancer compared with those of laparoscopic surgery. DESIGN We performed a single-center retrospective analysis. SETTING The data of a tertiary academic institution was reviewed. PATIENTS A total of 705 patients underwent laparoscopic (n = 415) or robotic (n = 118) low anterior resection for stage I to III mid/low rectal cancer. A total of 118 patients in each group were selected from the original data set by using propensity score matching. MAIN OUTCOME MEASURES The main outcomes were 5-year disease-free survival, distant recurrence, and local recurrence. RESULTS The 2 groups were balanced in terms of basic characteristics, perioperative treatment, and pathological stage. The 5-year disease-free survival rate was 80.5% in the laparoscopic group and 87.6% in the robotic group (p = 0.118). The 5-year distant recurrence rate and local recurrence rate were 19.0% and 4.2% in the laparoscopic group and 10.0% and 3.7% in the robotic group (p = 0.048 and p = 0.846). In a subgroup of patients who received preoperative chemoradiation and had ypT3/4 tumors, the 5-year distant recurrence and local recurrence rates were 44.8% and 5.0% in the laparoscopic group and 9.8% and 9.8% in the robotic group (p = 0.014 and p = 0.597). LIMITATIONS The retrospective nature of the study, potential selection bias with distinct demographics between the groups, and relatively small number of cases are limitations. CONCLUSIONS Robotic surgery for mid/low rectal cancer shows similar long-term oncologic outcomes with laparoscopic surgery but is beneficial to a certain group of patients with advanced rectal cancer with poor response to neoadjuvant chemoradiation. Additional studies are required to confirm our results. See Video Abstract at http://links.lww.com/DCR/B546. LA CIRUGA ROBTICA MUESTRA RESULTADOS ONCOLGICOS A LARGO PLAZO SIMILARES A LA CIRUGA LAPAROSCPICA EN CASOS DE CNCER DE RECTO MEDIO / BAJO, PERO ES VENTAJOSA EN CASOS YPT POSTQUIMIORADIOTERAPIA PREOPERATORIA ANTECEDENTES:Se desconoce la eficacia oncológica a largo plazo de la cirugía robótica en pacientes con cáncer de recto.OBJETIVO:La finalidad de nuestro estudio fue el investigar los resultados de supervivencia de la escisión mesorrectal total robótica en casos de cáncer de recto medio / bajo en comparación con los de la cirugía laparoscópica.DISEÑO:Realizamos un análisis retrospectivo mono-céntrico.AJUSTE:Se revisaron los datos de una institución académica terciaria.PACIENTES:705 pacientes fueron sometidos a resección anterior baja laparoscópica (n = 415) o robótica (n = 118) para cáncer de recto medio / bajo en estadio I-III. Se seleccionó un total de 118 pacientes en cada grupo del conjunto de datos original utilizando el emparejamiento por puntuación de propensión.RESULTADOS PRINCIPALES:Éstos fueron, la supervivencia libre de enfermedad a 5 años, la recurrencia a distancia y la recurrencia local.RESULTADOS:Los dos grupos estaban equilibrados en cuanto a características básicas, tratamiento péri-operatorio y estadío patológico. La tasa de sobrevida libre de enfermedad a 5 años fue del 80,5% en el grupo laparoscópico y del 87,6% en el grupo robótico (p = 0,118). La tasa de recurrencia a distancia a 5 años y la tasa de recurrencia local fueron 19,0% y 4,2% en el grupo laparoscópico y 10,0% y 3,7% en el grupo robótico, respectivamente (p = 0,048 y p= 0,846). En el subgrupo de pacientes que recibieron quimio-radioterapia pré-operatoria y tenían tumores ypT3-4, las tasas de recidiva a distancia a 5 años y recidiva local fueron 44,8% y 5,0% en el grupo laparoscópico y 9,8% y 9,8% en el grupo robótico, respectivamente (p = 0.014 y p = 0.597).LIMITACIONES:La naturaleza retrospectiva del estudio, el posible sesgo en la selección con datos demográficos distintos entre los grupos y un número relativamente pequeño de casos son limitaciones importantes.CONCLUSIONES:La cirugía robótica para el cáncer de recto medio / bajo muestra resultados oncológicos a largo plazo similares con la cirugía laparoscópica, pero es mas beneficiosa en ciertos grupos de cáncer de recto avanzado con mala respuesta a la quimio-radioterapia neoadyuvante. Se requieren más estudios para confirmar nuestros resultados. Consulte Video Resumen en http://links.lww.com/DCR/B546.).
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Affiliation(s)
- Soo Yeun Park
- Colorectal Cancer Center, Kyungpook National University Chilgok Hospital, Department of Surgery, School of Medicine, Kyungpook National University, Daegu, South Korea
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Weng X, Wei D, Yang Z, Pang W, Pang K, Gu B, Wei X. Photodynamic therapy reduces metastasis of breast cancer by minimizing circulating tumor cells. BIOMEDICAL OPTICS EXPRESS 2021; 12:3878-3886. [PMID: 34457386 PMCID: PMC8367230 DOI: 10.1364/boe.429947] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 05/12/2021] [Accepted: 05/15/2021] [Indexed: 06/13/2023]
Abstract
Cancer metastasis after traditional surgery introduces a high barrier to therapy efficacy. Photodynamic therapy (PDT) for cancer is based on a photochemical process of photosensitizers that concentrate in tumors and release oxidant species under light excitation to destroy cells. Compared with traditional surgery, PDT provides minimal invasion and targeted therapy. In this in vivo study, we monitor the real-time and long-term dynamics of circulating tumor cells (CTCs) after a single round of PDT and after surgical resection in a breast cancer animal model. The CTC level is low after PDT treatment, and the recurrence of the primary tumor is postponed in the PDT group compared with the resection group. We find that metastasis is correlated with the CTC level, and the PDT-treated mice show no metastasis in the lung or liver. Our results suggest PDT can effectively reduce metastasis by minimizing CTCs after treatment and is a great technology for breast cancer therapy.
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Affiliation(s)
- Xiaofu Weng
- School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China
| | - Dan Wei
- Key Laboratory of Oceanographic Big Data Mining and Application of Zhejiang Province, School of Information Engineering, Zhejiang Ocean University, Zhoushan, Zhejiang 316022, China
| | - Zhangru Yang
- Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, No. 241 West Huaihai Road, Shanghai 200030, China
| | - Wen Pang
- School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China
| | - Kai Pang
- School of Instrument Science and Opto Electronics Engineering of Beijing Information Science and Technology University, Beijing 100192, China
| | - Bobo Gu
- School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China
| | - Xunbin Wei
- School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China
- Biomedical Engineering Department, Peking University, Beijing, 100081, China
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China
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Watson J, Ninh MK, Ashford S, Cornett EM, Kaye AD, Urits I, Viswanath O. Anesthesia Medications and Interaction with Chemotherapeutic Agents. Oncol Ther 2021; 9:121-138. [PMID: 33861416 PMCID: PMC8140172 DOI: 10.1007/s40487-021-00149-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 03/13/2021] [Indexed: 02/07/2023] Open
Abstract
Cancer is now a leading health concern worldwide. In an effort to provide these patients with adequate care, coordination between anesthesiologists and surgeons is crucial. In cancer-related treatment, it is very clear that radio-chemotherapy and medical procedures are important. There are some obstacles to anesthesia when dealing with cancer treatment, such as physiological disturbances, tumor-related symptoms, and toxicity in traditional chemotherapy treatment. Therefore, it is important that a multisystemic, multidisciplinary and patient-centered approach is used to preserve perioperative homeostasis and immune function integrity. Adding adjuvants can help increase patient safety and satisfaction and improve clinical efficacy. Correctly paired anesthetic procedures and medications will reduce perioperative inflammatory and immune changes that could potentially contribute to improved results for future cancer patients. Further research into best practice strategies is required which will help to enhance the acute and long-term effects of cancer care in clinical practice.
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Affiliation(s)
- Jeremy Watson
- LSU Health Shreveport, 1501 Kings Hwy, Shreveport, LA 71103 USA
| | - Michael K. Ninh
- LSU Health Shreveport, 1501 Kings Hwy, Shreveport, LA 71103 USA
| | - Scott Ashford
- LSU Health Shreveport, 1501 Kings Hwy, Shreveport, LA 71103 USA
| | - Elyse M. Cornett
- Department of Anesthesiology, LSU Health Shreveport, 1501 Kings Highway, P.O. Box 33932, Shreveport, LA 71103 USA
| | - Alan David Kaye
- Departments of Anesthesiology and Pharmacology, Toxicology, and Neurosciences, LSU Health Shreveport, 1501 Kings Highway, Shreveport, LA 71103 USA
| | - Ivan Urits
- Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215 USA
| | - Omar Viswanath
- Department of Anesthesiology, Louisiana State University Shreveport, Shreveport, LA USA
- Valley Pain Consultants – Envision Physician Services, Phoenix, AZ USA
- Department of Anesthesiology, University of Arizona College of Medicine-Phoenix, Phoenix, AZ USA
- Department of Anesthesiology, Creighton University School of Medicine, Omaha, NE USA
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Lv X, Li X, Guo K, Li T, Yang Y, Lu W, Wang S, Liu S. Effects of Systemic Lidocaine on Postoperative Recovery Quality and Immune Function in Patients Undergoing Laparoscopic Radical Gastrectomy. DRUG DESIGN DEVELOPMENT AND THERAPY 2021; 15:1861-1872. [PMID: 33976537 PMCID: PMC8106403 DOI: 10.2147/dddt.s299486] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 03/26/2021] [Indexed: 12/09/2022]
Abstract
Objective This study aimed to explore the effects of lidocaine on postoperative quality of recovery (QoR) and immune function in patients undergoing laparoscopic radical gastrectomy. Methods In total, 135 patients were enrolled and were equally randomized to receive low-dose lidocaine (Group LL: 1.5 mg/kg bolus followed by an infusion at 1.0 mg/kg/hour) or high-dose lidocaine (Group HL: 1.5 mg/kg bolus followed by an infusion at 2.0 mg/kg/hour) or Controls (Group C: received a volume-matched normal saline at the same rate). The primary outcome was a QoR-40 score on postoperative day (POD) 1. Secondary outcomes were a QoR-40 score on POD 3, levels of inflammatory factors (IL-6, IL-10, TNF-α) and CD4+T cells, CD8+T cells proportions, and CD4+/CD8+ cell ratios and postoperative recovery of bowel function. Results There were no statistically significant differences in patient characteristics at baseline. The total QoR-40 scores on POD 1 in Group HL (171.4±3.89) were higher than those in Group LL (166.20±4.05) and in Group C (163.40±4.38) (adjusted P<0.001). Differences in the dimension scores of QoR-40 for pain, physical comfort, and emotional state were significant across the three groups. Lidocaine administration significantly reduced the release of IL-6, IL-10, TNF-α, and attenuated immune changes induced by trauma. Kaplan–Meier curves showed that the median time to the first exhaust and defecation were shorter in the Group HL than in Groups LL and C (1.55 days vs 2.4 days vs 2.6 days, log rank P<0.0001; and 2.86 days vs 3.22 days vs 3.46 days, log rank P=0.002, respectively). Additionally, patients in lidocaine groups required less remifentanil consumption and experienced lower pain intensity, compared with the control group. Conclusion Systemic lidocaine improved postoperative recovery, alleviated inflammation and immunosuppression, and accelerated the return of bowel function, and is thus, worthy of clinical application. Clinical Trials Registration ChiCTR2000028934.
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Affiliation(s)
- Xueli Lv
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China
| | - Xiaoxiao Li
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China
| | - Kedi Guo
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China
| | - Tong Li
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China
| | - Yuping Yang
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China
| | - Wensi Lu
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China
| | - Shuting Wang
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China
| | - Su Liu
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China.,Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China
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Grahn O, Lundin M, Lydrup ML, Angenete E, Rutegård M. Postoperative non-steroidal anti-inflammatory drug use and oncological outcomes of rectal cancer. BJS Open 2021; 5:6137422. [PMID: 33609397 PMCID: PMC7893477 DOI: 10.1093/bjsopen/zraa050] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Accepted: 11/06/2020] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Non-steroidal anti-inflammatory drugs (NSAIDs) are known to suppress the inflammatory response after surgery and are often used for pain control. This study aimed to investigate NSAID use after radical surgical resection for rectal cancer and long-term oncological outcomes. METHODS A cohort of patients who underwent anterior resection for rectal cancer between 2007 and 2013 in 15 hospitals in Sweden was investigated retrospectively. Data were obtained from the Swedish Colorectal Cancer Registry and medical records; follow-up was undertaken until July 2019. Patients who received NSAID treatment for at least 2 days after surgery were compared with controls who did not, and the primary outcome was recurrence-free survival. Cox regression modelling with confounder adjustment, propensity score matching, and an instrumental variables approach were used; missing data were handled by multiple imputation. RESULTS The cohort included 1341 patients, 362 (27.0 per cent) of whom received NSAIDs after operation. In analyses using conventional regression and propensity score matching, there was no significant association between postoperative NSAID use and recurrence-free survival (adjusted hazard ratio (HR) 1.02, 0.79 to 1.33). The instrumental variables approach, including individual hospital as the instrumental variable and clinicopathological variables as co-variables, suggested a potential improvement in the NSAID group (HR 0.61, 0.38 to 0.99). CONCLUSION conventional modelling did not demonstrate an association between postoperative NSAID use and recurrence-free survival in patients with rectal cancer, although an instrumental variables approach suggested a potential benefit.
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Affiliation(s)
- O Grahn
- Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden
| | - M Lundin
- Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden.,Department of Statistics, Umeå School of Business, Economics and Statistics, Umeå University, Umeå, Sweden
| | - M-L Lydrup
- Department of Surgery, Skåne University Hospital, Malmö, Lund University, Lund, Sweden
| | - E Angenete
- Department of Surgery, Institute of Clinical Sciences, Scandinavian Surgical Outcomes Research Group, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.,Region Västra Götaland, Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - M Rutegård
- Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden.,Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden
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Hochman G, Shacham-Shmueli E, Raskin SP, Rosenbaum S, Bunimovich-Mendrazitsky S. Metastasis Initiation Precedes Detection of Primary Cancer-Analysis of Metastasis Growth in vivo in a Colorectal Cancer Test Case. Front Physiol 2021; 11:533101. [PMID: 33391005 PMCID: PMC7773782 DOI: 10.3389/fphys.2020.533101] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Accepted: 11/20/2020] [Indexed: 11/16/2022] Open
Abstract
Most cases of deaths from colorectal cancer (CRC) result from metastases, which are often still undetectable at disease detection time. Even so, in many cases, shedding is assumed to have taken place before that time. The dynamics of metastasis formation and growth are not well-established. This work aims to explore CRC lung metastasis growth rate and dynamics. We analyzed a test case of a metastatic CRC patient with four lung metastases, with data of four serial computed tomography (CT) scans measuring metastasis sizes while untreated. We fitted three mathematical growth models—exponential, logistic, and Gompertzian—to the CT measurements. For each metastasis, a best-fitted model was determined, tumor doubling time (TDT) was assessed, and metastasis inception time was extrapolated. Three of the metastases showed exponential growth, while the fourth showed logistic restraint of the growth. TDT was around 93 days. Predicted metastasis inception time was at least 4–5 years before the primary tumor diagnosis date, though they did not reach detectable sizes until at least 1 year after primary tumor resection. Our results support the exponential growth approximation for most of the metastases, at least for the clinically observed time period. Our analysis shows that metastases can be initiated before the primary tumor is detectable and implies that surgeries accelerate metastasis growth.
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Affiliation(s)
- Gili Hochman
- Department of Mathematics, Ariel University, Ariel, Israel
| | | | | | - Sara Rosenbaum
- Department of Mathematics, Ariel University, Ariel, Israel
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Abstract
Metastatic dissemination occurs very early in the malignant progression of a cancer but the clinical manifestation of metastases often takes years. In recent decades, 5-year survival of patients with many solid cancers has increased due to earlier detection, local disease control and adjuvant therapies. As a consequence, we are confronted with an increase in late relapses as more antiproliferative cancer therapies prolong disease courses, raising questions about how cancer cells survive, evolve or stop growing and finally expand during periods of clinical latency. I argue here that the understanding of early metastasis formation, particularly of the currently invisible phase of metastatic colonization, will be essential for the next stage in adjuvant therapy development that reliably prevents metachronous metastasis.
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Affiliation(s)
- Christoph A Klein
- Experimental Medicine and Therapy Research, University of Regensburg, Regensburg, Germany.
- Division of Personalized Tumor Therapy, Fraunhofer Institute for Toxicology and Experimental Medicine, Regensburg, Germany.
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Pedone Anchora L, Bizzarri N, Kucukmetin A, Turco LC, Gallotta V, Carbone V, Rundle S, Ratnavelu N, Cosentino F, Chiantera V, Fagotti A, Fedele C, Gomes N, Ferrandina G, Scambia G. Investigating the possible impact of peritoneal tumor exposure amongst women with early stage cervical cancer treated with minimally invasive approach. Eur J Surg Oncol 2020; 47:1090-1097. [PMID: 33039294 DOI: 10.1016/j.ejso.2020.09.038] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 09/03/2020] [Accepted: 09/21/2020] [Indexed: 12/16/2022] Open
Abstract
INTRODUCTION Recent findings show a detrimental impact of the minimally invasive approach on patients with early stage cervical cancer (ECC). Reasons beyond these results are unclear. The aim of the present article is to investigate the possible role of peritoneal contamination during intracorporeal colpotomy. METHODS patients with early stage cervical cancer were divided into 2 groups: no intraperitoneal exposure (N-IPE) intraperitoneal exposure (IPE) during minimally invasive surgery. Patients of the 2 groups were propensity-matched according to the major risk factors. RESULTS 226 cases of the IPE group had a significant worst prognosis than the 142 cases of the N-IPE group (4.5-years disease free survival: 86.6% vs 95.9% respectively, p = 0.005), while N-IPE had similar survival to open surgery (4.5-years disease free survival: 95.0% vs 90.5% respectively, p = 0.164). Distant recurrence was more frequent among IPE patients with a borderline significance (3.5% vs 0.4% among IPE and N-IPE respectively, p = 0.083). On multivariate analysis, intraperitoneal tumor exposure was an independent prognostic factors for worse survival; patients belonging to the N-IPE group had a risk of recurrence of about 3-fold lower compared to patients of the IPE group (hazard ratio: 0.37, 95% confidence interval: 0.15-0.88, p = 0.025). CONCLUSION it would be advisable that further prospective studies investigating the efficacy of different surgical approach in ECC take into consideration of this issue. Moreover, all other measures that could potentially prevent peritoneal exposure of tumor should be adopted during minimally invasive surgery for early stage cervical cancer to provide higher survival outcomes.
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Affiliation(s)
- Luigi Pedone Anchora
- Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Roma, Italy
| | - Nicolò Bizzarri
- Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Roma, Italy.
| | - Ali Kucukmetin
- Northern Gynaecological Oncology Center, Queen Elizabeth Hospital, Gateshead, United Kingdom
| | - Luigi Carlo Turco
- Gemelli Molise, Dipartimento di Oncologia, UOC Ginecologia Oncologica, Campobasso, Italy; Gynecology and Brest Care Unit, Mater Olbia Hospital, Olbia, Italy
| | - Valerio Gallotta
- Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Roma, Italy
| | - Vittoria Carbone
- Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Roma, Italy
| | - Stuart Rundle
- Northern Gynaecological Oncology Center, Queen Elizabeth Hospital, Gateshead, United Kingdom
| | - Nithya Ratnavelu
- Northern Gynaecological Oncology Center, Queen Elizabeth Hospital, Gateshead, United Kingdom
| | - Francesco Cosentino
- Gemelli Molise, Dipartimento di Oncologia, UOC Ginecologia Oncologica, Campobasso, Italy
| | - Vito Chiantera
- Department of Gynecologic Oncology, University of Palermo, Palermo, Italy
| | - Anna Fagotti
- Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Roma, Italy; Università Cattolica del Sacro Cuore, Roma, Italy
| | - Camilla Fedele
- Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Roma, Italy
| | - Nana Gomes
- Northern Gynaecological Oncology Center, Queen Elizabeth Hospital, Gateshead, United Kingdom
| | - Gabriella Ferrandina
- Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Roma, Italy; Università Cattolica del Sacro Cuore, Roma, Italy
| | - Giovanni Scambia
- Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Roma, Italy; Università Cattolica del Sacro Cuore, Roma, Italy
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Sevoflurane downregulates insulin-like growth factor-1 to inhibit cell proliferation, invasion and trigger apoptosis in glioma through the PI3K/AKT signaling pathway. Anticancer Drugs 2020; 30:e0744. [PMID: 31305291 DOI: 10.1097/cad.0000000000000744] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Sevoflurane is a new type of inhalation anesthetic used widely in the clinic. It has the characteristics of rapid induction, rapid recovery, and less irritative to the airway. Studies have shown that sevoflurane can affect the invasion and migration of a variety of malignant tumors. However, its effects on human glioma cells and related mechanisms are not clear. Cultured U251 and U87 cells were pretreated with sevoflurane. The effect of sevoflurane on proliferation was evaluated by MTT, and cell migration assay, cell apoptosis, and invasion ability were evaluated by wound-healing assay, cell apoptosis, and Transwell assays. Insulin-like growth factor-1 (IGF-1) and PI3K/AKT signaling pathway gene expression in sevoflurane-treated cell lines was measured by western blotting analysis, respectively. 5% sevoflurane significantly inhibited proliferation ability in both U251 and U87 cells. Sevoflurane inhibited glioma cells invasion and migration, and promoted apoptosis. Sevoflurane inhibited IGF-1 and promoted the expression of apoptosis-related proteins in glioma cells. In addition, sevoflurane inhibited the PI3K/AKT signaling pathway in glioma cells. This study clarifies that sevoflurane inhibits proliferation, invasion, and migration, and promotes apoptosis in glioma cells. These effects are regulated by IGF-1, an upstream gene of the PI3K/AKT signaling pathway. These findings may be significant for the selection of anesthetic agents in glioma surgery to improve the prognosis of patients.
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Clinical outcomes and prognostic factors of robotic assisted rectal cancer resection alone versus robotic rectal cancer resection with natural orifice extraction: a matched analysis. Sci Rep 2020; 10:12848. [PMID: 32733103 PMCID: PMC7392890 DOI: 10.1038/s41598-020-69830-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 07/20/2020] [Indexed: 12/14/2022] Open
Abstract
Robotic rectal cancer resection with natural orifice extraction is a recently developed minimally invasive surgery used in the treatment of patients with rectal cancer. However, its safety and feasibility remain undiscussed and controversial. This study reported the clinical outcomes and prognostic factors pertaining to traditional robotic assisted rectal cancer resection alone against that of robotic rectal cancer resection with natural orifice extraction to provide a discussion on this issue. 49 patients who underwent robotic rectal cancer resection with natural orifice extraction and 49 matched patients who underwent conventional robotic assisted rectal cancer resection were systematically analyzed in this study. Regarding the baseline characteristics, after matching, no significant differences were observed between the natural orifice specimen extraction (NOSE) group and the robotic assisted rectal cancer resection (RARC) group. Patients in the NOSE group had a reduced visual analog scale (p < 0.001), passed flatus more quickly (p = 0.002) and suffered less surgical stress than those in the RARC group. Moreover, 4 complications were observed in the NOSE group and 7 complications in the RARC group with no significant difference (p = 0.337) in terms of complications. The two groups had a similar survival outcomes, where the 3-year overall survival (p = 0.738) and 3-year progression-free survival (p = 0.986) were all comparable between the two groups. Histological differentiation and T stage could be regarded as independent prognostic factors for 3-year overall survival and 3-year progression-free survival. Robotic rectal cancer resection with natural orifice extraction is a safe and feasible minimally invasive surgery for patients suffering from rectal cancer as it encompasses considerable several advantages. Histological differentiation and T stage may serve as independent prognostic factors for 3-year overall survival and 3-year progression-free survival.
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Phosphodiesterase-5 inhibitors use and risk for mortality and metastases among male patients with colorectal cancer. Nat Commun 2020; 11:3191. [PMID: 32581298 PMCID: PMC7314744 DOI: 10.1038/s41467-020-17028-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Accepted: 06/04/2020] [Indexed: 02/03/2023] Open
Abstract
Phosphodiesterase-5 (PDE5) inhibitors are suggested to have anti-tumor effects and to inhibit surgery-induced immunosuppression. We aimed to explore whether post-diagnostic use of PDE5 inhibitors was associated with a better prognosis among male patients with colorectal cancer (CRC) and the role of open surgery in the association. Here we show that post-diagnostic use of PDE5 inhibitors is associated with a decreased risk of CRC-specific mortality (adjusted HR = 0.82, 95% CI 0.67-0.99) as well as a decreased risk of metastasis (adjusted HR = 0.85, 95% CI 0.74-0.98). Specifically, post-operative use of PDE5 inhibitors has a strong anti-cancer effect. The reduced risk of metastasis is mainly due to distant metastasis but not regional lymphatic metastasis. PDE5 inhibitors have the potential to be an adjuvant drug for patients with CRC to improve prognosis, especially those who have undergone open surgery. Phosphodiesterase-5 (PDE5) inhibitors have been suggested to have an anti-tumor effect and block surgery-induced immunosuppression. Here, the authors show that postdiagnostic use of PDE5 inhibitors is associated with a decreased risk of colorectal cancerspecific mortality as well as a decreased risk of metastasis.
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Han CJ, Gigic B, Schneider M, Kulu Y, Peoples AR, Ose J, Kölsch T, Jacobsen PB, Colditz GA, Figueiredo JC, Grady WM, Li CI, Shibata D, Siegel EM, Toriola AT, Ulrich AB, Syrjala KL, Ulrich CM. Risk factors for cancer-related distress in colorectal cancer survivors: one year post surgery. J Cancer Surviv 2020; 14:305-315. [PMID: 32166576 PMCID: PMC7261242 DOI: 10.1007/s11764-019-00845-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Accepted: 12/01/2019] [Indexed: 01/12/2023]
Abstract
PURPOSES Cancer-related distress is known to persist long after completion of treatment. Factors related to distress are largely unexplored in colorectal cancer (CRC) survivors. We examined changes over time and risk factors for distress in CRC patients over the first year after surgery. METHODS We included 212 CRC patients with data at 6 and 12 months post-surgery from the ColoCare Study in Heidelberg, Germany. Sociodemographic and lifestyle factors, social support, and health-related quality of life (HrQOL) prior to surgery were evaluated as predictors of cancer-related distress. Distress was measured with the Cancer and Treatment Distress instrument (CTXD). Linear regression analyses examined associations between risk factors and distress. RESULTS Distress subscale scores varied significantly over time: health burden subscale score increased (P < .001), while finances (P = .004), medical demands (P < .001), and identity (P < .001) subscale scores decreased over time. Uncertainty and family strain subscale scores did not change. Younger age, lower income, advanced tumor stage, poorer social support, and poorer baseline HrQOL predicted higher level distress at 6 and 12 months. CONCLUSION Cancer-related distress continues unresolved after surgery. Although some risk factors are difficult to alter, those at highest risk can be identified earlier for possible preventive strategies. IMPLICATIONS FOR CANCER SURVIVORS Screening for risk factors pre-surgery would allow for targeted interventions including strategies to improve resources for those with low support, thereby reducing long-term distress in CRC survivors.
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Affiliation(s)
- Claire J Han
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Biljana Gigic
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany.
| | - Martin Schneider
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Yakup Kulu
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Anita R Peoples
- Division of Population Sciences, Huntsman Cancer Institute, Salt Lake City, Utah, USA
- Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA
| | - Jennifer Ose
- Division of Population Sciences, Huntsman Cancer Institute, Salt Lake City, Utah, USA
- Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA
| | - Torsten Kölsch
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Paul B Jacobsen
- Healthcare Delivery Research Program, National Cancer Institute, Bethesda, MD, USA
| | - Graham A Colditz
- Department of Surgery, Division of Public Health Sciences, Washington University School of Medicine and Siteman Cancer Center, St. Louis, MO, USA
| | - Jane C Figueiredo
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, California, LA, USA
| | - William M Grady
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
- Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Christopher I Li
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - David Shibata
- Department of Surgery, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Erin M Siegel
- Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Adetunji T Toriola
- Department of Surgery, Division of Public Health Sciences, Washington University School of Medicine and Siteman Cancer Center, St. Louis, MO, USA
| | - Alexis B Ulrich
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Karen L Syrjala
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
| | - Cornelia M Ulrich
- Division of Population Sciences, Huntsman Cancer Institute, Salt Lake City, Utah, USA.
- Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
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Díaz-Cambronero O, Mazzinari G, Giner F, Belltall A, Ruiz-Boluda L, Marqués-Marí A, Sánchez-Guillén L, Eroles P, Cata JP, Argente-Navarro MP. Mu Opioid Receptor 1 (MOR-1) Expression in Colorectal Cancer and Oncological Long-Term Outcomes: A Five-Year Retrospective Longitudinal Cohort Study. Cancers (Basel) 2020; 12:cancers12010134. [PMID: 31948099 PMCID: PMC7016725 DOI: 10.3390/cancers12010134] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Revised: 01/01/2020] [Accepted: 01/02/2020] [Indexed: 12/17/2022] Open
Abstract
Preclinical evidence has shown increased expression of mu opioid receptor 1 (MOR-1) in colorectal cancer although its association with disease-free and overall survival (DFS and OS) has not been investigated. We hypothesized that MOR-1 was overexpressed in tumor samples compared to normal tissue and this was associated with decreased DFS and OS. We carried out a retrospective study assessing the association of MOR-1 tumor expression with long-term outcomes by immunohistochemistry in normal and tumor samples from 174 colorectal cancer patients. The primary endpoint was five years of DFS. Secondary endpoints were five years of OS, the difference in MOR-1 expression between normal and tumor tissue and the occurrence of postoperative complications. Multivariable Cox regression showed no significant association between MOR-1 expression and DFS (HR 0.791, 95% CI 0.603–1.039, p = 0.092). MOR-1 expression was higher in tumor tissue compared to non-tumor tissue. No associations were found between MOR-1 expression and OS or postoperative complications. These findings suggest that although MOR-1 is over-expressed in colorectal cancer samples there is no association to increased risk of recurrence or mortality. Future studies are warranted to elucidate the role of cancer stage, genetic polymorphism, and quantitative assessment of MOR-1 over-expression on long-term outcomes in colorectal cancer.
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Affiliation(s)
- Oscar Díaz-Cambronero
- Department of Anesthesiology, Hospital Universitarii Politécnic La Fe, Avenida de Fernando Abril Martorell, 106, 46026 Valencia, Spain
- Perioperative Medicine Research Group, Instituto de Investigación Sanitaria La Fe (IISlaFe), Avenida de Fernando Abril Martorell, 106, 46026 Valencia, Spain
- EU-COST Action 15204, Euro-Periscope, Avenue Louise 149, 1050 Brussels, Belgium
- Correspondence:
| | - Guido Mazzinari
- Department of Anesthesiology, Hospital Universitarii Politécnic La Fe, Avenida de Fernando Abril Martorell, 106, 46026 Valencia, Spain
- Perioperative Medicine Research Group, Instituto de Investigación Sanitaria La Fe (IISlaFe), Avenida de Fernando Abril Martorell, 106, 46026 Valencia, Spain
- EU-COST Action 15204, Euro-Periscope, Avenue Louise 149, 1050 Brussels, Belgium
| | - Francisco Giner
- Department of Pathology, Hospital Universitari i Politécnic La Fe, Avenida de Fernando Abril Martorell, 106, 46026 Valencia, Spain
| | - Amparo Belltall
- Department of Anesthesiology, Hospital Universitarii Politécnic La Fe, Avenida de Fernando Abril Martorell, 106, 46026 Valencia, Spain
| | - Lola Ruiz-Boluda
- Department of Anesthesiology, Hospital Universitarii Politécnic La Fe, Avenida de Fernando Abril Martorell, 106, 46026 Valencia, Spain
| | - Anabel Marqués-Marí
- Department of Anesthesiology, Hospital Universitarii Politécnic La Fe, Avenida de Fernando Abril Martorell, 106, 46026 Valencia, Spain
- Perioperative Medicine Research Group, Instituto de Investigación Sanitaria La Fe (IISlaFe), Avenida de Fernando Abril Martorell, 106, 46026 Valencia, Spain
- EU-COST Action 15204, Euro-Periscope, Avenue Louise 149, 1050 Brussels, Belgium
| | - Luis Sánchez-Guillén
- Department of Digestive Surgery, Hospital General Universitario de Elche, Calle Almazara, 11, 03203 Elche, Spain
| | - Pilar Eroles
- EU-COST Action 15204, Euro-Periscope, Avenue Louise 149, 1050 Brussels, Belgium
- INCLIVA Biomedical Research Institute, Avenida de Menéndez y Pelayo, 4, 46010 Valencia, Spain
- Department Medical Oncology, University of Valencia INCLIVA-Hospital Clínico de Valencia-CIBERONC, Avenida de Menéndezy Pelayo, 4, 46010 Valencia, Spain
| | - Juan Pablo Cata
- Department of Anesthesiology & Perioperative Medicine, The University of Texas–MD Anderson Cancer Center, Houston, TX 77030, USA
- Anesthesia & Surgical Oncology Research Group, Houston, TX 77030, USA
| | - María Pilar Argente-Navarro
- Department of Anesthesiology, Hospital Universitarii Politécnic La Fe, Avenida de Fernando Abril Martorell, 106, 46026 Valencia, Spain
- Perioperative Medicine Research Group, Instituto de Investigación Sanitaria La Fe (IISlaFe), Avenida de Fernando Abril Martorell, 106, 46026 Valencia, Spain
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Raskov H, Orhan A, Salanti A, Gögenur I. Premetastatic niches, exosomes and circulating tumor cells: Early mechanisms of tumor dissemination and the relation to surgery. Int J Cancer 2020; 146:3244-3255. [PMID: 31808150 DOI: 10.1002/ijc.32820] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 11/15/2019] [Accepted: 11/29/2019] [Indexed: 12/12/2022]
Abstract
The physiological stress response to surgery promotes wound healing and functional recovery and includes the activation of neural, inflammatory and proangiogenic signaling pathways. Paradoxically, the same pathways also promote metastatic spread and growth of residual cancer. Human and animal studies show that cancer surgery can increase survival, migration and proliferation of residual tumor cells. To secure the survival and growth of disseminated tumor cells, the formation of premetastatic niches in target organs involves a complex interplay between microenvironment, immune system, circulating tumor cells, as well as chemical mediators and exosomes secreted by the primary tumor. This review describes the current understanding of the early mechanisms of dissemination, as well as how surgery may facilitate disease progression.
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Affiliation(s)
- Hans Raskov
- Center for Surgical Science, Zealand University Hospital, Køge, Denmark
| | - Adile Orhan
- Center for Surgical Science, Zealand University Hospital, Køge, Denmark.,Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Ali Salanti
- Centre for Medical Parasitology at Department of Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark
| | - Ismail Gögenur
- Center for Surgical Science, Zealand University Hospital, Køge, Denmark.,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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Bashir Mohamed K, Hansen CH, Krarup PM, Fransgård T, Madsen MT, Gögenur I. The impact of anastomotic leakage on recurrence and long-term survival in patients with colonic cancer: A systematic review and meta-analysis. Eur J Surg Oncol 2019; 46:439-447. [PMID: 31727475 DOI: 10.1016/j.ejso.2019.10.038] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Accepted: 10/29/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND/OBJECTIVE Anastomotic leakage (AL) is one of the most severe complications following colorectal cancer surgery and is associated with increased short and long term mortality. The literature is conflicting regarding increased risk of recurrence after AL. The aim of this study was to systematically review the impact of anastomotic leakage on the risk of local or distant recurrence and overall survival, cancer specific survival, and disease-free survival. METHODS A systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. A systematic search in PubMed, EMBASE, CINHAL, and The Cochrane Library was performed and meta-analyses were performed on all outcomes including analysis based on time-to-event data. RESULTS A total of eighteen cohort studies, including 69,047 patients whereof 2,555 patients had anastomotic leakage, were included. Meta-analysis demonstrated no significant effects of anastomotic leakage on local recurrence (RR 1.16, 95% CI 0.84-1.59) or distant recurrence (RR 1.44, 95% CI 0.52-3.96). Anastomotic leakage decreased overall survival (RR 0.85, 95% CI 0.77-0.94), disease free survival (RR 0.80, 95% CI 0.72-0.89), and cancer specific survival (RR 0.90, 95% CI 0.83-0.97). A time-to-event analysis was conducted on available data and the results were congruent with the frequency analyses. CONCLUSION Anastomotic leakage following colonic resections is significantly associated with impaired overall survival, disease free survival and cancer specific survival. The study did not show any statistically significant association between anastomotic leakage and recurrence.
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Affiliation(s)
- Khadra Bashir Mohamed
- Center for Surgical Science, Department of Surgery, Zealand University Hospital, Lykkebaekvej 1, 4600, Koege, Denmark.
| | - Christine Haangard Hansen
- Center for Surgical Science, Department of Surgery, Zealand University Hospital, Lykkebaekvej 1, 4600, Koege, Denmark
| | - Peter-Martin Krarup
- Center for Surgical Science, Department of Surgery, Zealand University Hospital, Lykkebaekvej 1, 4600, Koege, Denmark
| | - Tina Fransgård
- Center for Surgical Science, Department of Surgery, Zealand University Hospital, Lykkebaekvej 1, 4600, Koege, Denmark
| | - Michael Tvilling Madsen
- Center for Surgical Science, Department of Surgery, Zealand University Hospital, Lykkebaekvej 1, 4600, Koege, Denmark
| | - Ismail Gögenur
- Center for Surgical Science, Department of Surgery, Zealand University Hospital, Lykkebaekvej 1, 4600, Koege, Denmark; Institute of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, Denmark
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Klapdor R, Hertel H, Hillemanns P, Röttger M, Soergel P, Kuehnle E, Jentschke M. Peritoneal contamination with ICG-stained cervical secretion as surrogate for potential cervical cancer tumor cell dissemination: A proof-of-principle study for laparoscopic hysterectomy. Acta Obstet Gynecol Scand 2019; 98:1398-1403. [PMID: 31242322 DOI: 10.1111/aogs.13681] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Revised: 05/26/2019] [Accepted: 06/18/2019] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Intracorporal colpotomy during radical hysterectomy for cervical cancer is discussed to be a risk factor for peritoneal dissemination of tumor cells. It might lead to increased recurrence rates after laparoscopic radical hysterectomy compared with abdominal hysterectomy, as shown by the recent LACC study. Data on the frequency or mechanisms of peritoneal contamination are missing. We aimed to analyze peritoneal contamination of cervical secretion during intracorporal colpotomy with a novel indocyaningreen (ICG)-based technique. MATERIAL AND METHODS In this prospective proof-of-principle study, patients undergoing routine laparoscopic or robot-assisted hysterectomy were selected. ICG was specifically applied to the cervical surface and routine surgery was performed. During colpotomy, pictures under white and fluorescence light were taken to evaluate frequency of contamination. RESULTS By using cervically applied ICG we were able to visualize directly peritoneal contamination with cervical secretion during intracorporal colpotomy. We detected peritoneal contamination in 9/12 (75%) patients undergoing routine laparoscopic hysterectomy. Contamination of laparoscopic instruments occurred in 60% of the patients. When contamination occurred, it was routinely detectable during all steps of colpotomy. There were no adverse effects during surgery. CONCLUSIONS Peritoneal contamination with cervical secretion frequently occurs during intracorporal colpotomy. This novel technique represents a promising tool for feasible and direct visualization of peritoneal contamination during colpotomy. The technique may be easily implemented in further studies on laparoscopic and abdominal hysterectomy and serve as a quality assessment tool for surgeons and surgical techniques.
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Affiliation(s)
- Rüdiger Klapdor
- Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany
| | - Hermann Hertel
- Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany
| | - Peter Hillemanns
- Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany
| | - Marlene Röttger
- Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany
| | - Philipp Soergel
- Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany
| | - Elna Kuehnle
- Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany
| | - Matthias Jentschke
- Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany
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Liaw CC, Liao TY, Tsui KH, Juan YH. Survival Benefit for Patients With Metastatic Urothelial Carcinoma Receiving Continuous Maintenance Chemotherapy. In Vivo 2019; 33:1249-1262. [PMID: 31280216 DOI: 10.21873/invivo.11597] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2019] [Revised: 05/28/2019] [Accepted: 06/03/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND/AIM Urothelial carcinoma is a chemo-sensitive cancer. We investigated the contributory factors to survival benefit of metastatic urothelial carcinoma (MUC) patients receiving continuous maintenance chemotherapy. PATIENTS AND METHODS Inclusion criteria were: i) pathology-confirmed urothelial carcinoma, ii) metastatic lesions identified mainly on pre-therapy computed tomography (CT) scans, and iii) inpatient-administered chemotherapy of at least three cycles. Chemotherapy regimens included 5-fluorouracil, leucovorin, cisplatin, and gemcitabine. RESULTS A total of 139 cases were enrolled in this study. The overall objective response rate was 60% and the median survival time was 17 months. Eight-two (59%) patients had inflammation-related symptoms following the course of chemotherapy. Fifty-five (41%) patients survived more than two years. All patients exhibited various fibrosis formations. No patient experienced unfavorable metastatic conditions. Inflammation-related symptoms remained in 28 (51%) patients. We found that surgery, invasive procedures, and infection likely led to a rapid tumor progression. CONCLUSION Continuous maintenance chemotherapy targeting chemo-sensitive tumors, administered at metronomic intervals and focus on tumor microenvironment, can increase MUC survival benefits.
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Affiliation(s)
- Chuang-Chi Liaw
- Division of Hemato-Oncology, Department of Internal Medicine Chang-Gung Memorial Hospital and Chang-Gung University College of Medicine, Taoyuan, Taiwan, R.O.C.
| | - Tzu-Yao Liao
- Division of Hemato-Oncology, Department of Internal Medicine Chang-Gung Memorial Hospital and Chang-Gung University College of Medicine, Taoyuan, Taiwan, R.O.C
| | - Ke-Hung Tsui
- Department of Urology, Chang-Gung Memorial Hospital and Chang-Gung University College of Medicine, Taoyuan, Taiwan, R.O.C
| | - Yu-Hsiang Juan
- Department of Medical Imaging and Intervention, Chang-Gung Memorial Hospital and Chang-Gung University College of Medicine, Taoyuan, Taiwan, R.O.C
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Hanns P, Paczulla AM, Medinger M, Konantz M, Lengerke C. Stress and catecholamines modulate the bone marrow microenvironment to promote tumorigenesis. Cell Stress 2019; 3:221-235. [PMID: 31338489 PMCID: PMC6612892 DOI: 10.15698/cst2019.07.192] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
High vascularization and locally secreted factors make the bone marrow (BM) microenvironment particularly hospitable for tumor cells and bones to a preferred metastatic site for disseminated cancer cells of different origins. Cancer cell homing and proliferation in the BM are amongst other regulated by complex interactions with BM niche cells (e.g. osteoblasts, endothelial cells and mesenchymal stromal cells (MSCs)), resident hematopoietic stem and progenitor cells (HSPCs) and pro-angiogenic cytokines leading to enhanced BM microvessel densities during malignant progression. Stress and catecholamine neurotransmitters released in response to activation of the sympathetic nervous system (SNS) reportedly modulate various BM cells and may thereby influence cancer progression. Here we review the role of catecholamines during tumorigenesis with particular focus on pro-tumorigenic effects mediated by the BM niche.
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Affiliation(s)
- Pauline Hanns
- Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland
| | - Anna M Paczulla
- Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland
| | - Michael Medinger
- Division of Clinical Hematology, University Hospital Basel, Basel, Switzerland
| | - Martina Konantz
- Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland
| | - Claudia Lengerke
- Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.,Division of Clinical Hematology, University Hospital Basel, Basel, Switzerland
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The Effect of Anaesthetic and Analgesic Technique on Oncological Outcomes. CURRENT ANESTHESIOLOGY REPORTS 2018. [DOI: 10.1007/s40140-018-0299-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Hashemi Goradel N, Najafi M, Salehi E, Farhood B, Mortezaee K. Cyclooxygenase-2 in cancer: A review. J Cell Physiol 2018; 234:5683-5699. [PMID: 30341914 DOI: 10.1002/jcp.27411] [Citation(s) in RCA: 505] [Impact Index Per Article: 72.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2018] [Accepted: 08/22/2018] [Indexed: 12/17/2022]
Abstract
Cyclooxygenase-2 (COX-2) is frequently expressed in many types of cancers exerting a pleiotropic and multifaceted role in genesis or promotion of carcinogenesis and cancer cell resistance to chemo- and radiotherapy. COX-2 is released by cancer-associated fibroblasts (CAFs), macrophage type 2 (M2) cells, and cancer cells to the tumor microenvironment (TME). COX-2 induces cancer stem cell (CSC)-like activity, and promotes apoptotic resistance, proliferation, angiogenesis, inflammation, invasion, and metastasis of cancer cells. COX-2 mediated hypoxia within the TME along with its positive interactions with YAP1 and antiapoptotic mediators are all in favor of cancer cell resistance to chemotherapeutic drugs. COX-2 exerts most of the functions through its metabolite prostaglandin E2. In some and limited situations, COX-2 may act as an antitumor enzyme. Multiple signals are contributed to the functions of COX-2 on cancer cells or its regulation. Members of mitogen-activated protein kinase (MAPK) family, epidermal growth factor receptor (EGFR), and nuclear factor-κβ are main upstream modulators for COX-2 in cancer cells. COX-2 also has interactions with a number of hormones within the body. Inhibition of COX-2 provides a high possibility to exert therapeutic outcomes in cancer. Administration of COX-2 inhibitors in a preoperative setting could reduce the risk of metastasis in cancer patients. COX-2 inhibition also sensitizes cancer cells to treatments like radio- and chemotherapy. Chemotherapeutic agents adversely induce COX-2 activity. Therefore, choosing an appropriate chemotherapy drugs along with adjustment of the type and does for COX-2 inhibitors based on the type of cancer would be an effective adjuvant strategy for targeting cancer.
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Affiliation(s)
- Nasser Hashemi Goradel
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoud Najafi
- Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Eniseh Salehi
- Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Bagher Farhood
- Departments of Medical Physics and Radiology, Faculty of Paramedical Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Keywan Mortezaee
- Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
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49
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Pasquier J, Vidal F, Hoarau-Véchot J, Bonneau C, Daraï E, Touboul C, Rafii A. Surgical peritoneal stress creates a pro-metastatic niche promoting resistance to apoptosis via IL-8. J Transl Med 2018; 16:271. [PMID: 30285881 PMCID: PMC6171219 DOI: 10.1186/s12967-018-1643-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Accepted: 09/24/2018] [Indexed: 12/14/2022] Open
Abstract
Background The mainstay of treatment of advanced ovarian cancer (AOC) involves chemotherapy, and debulking surgery. However, despite optimal surgical procedure and adjuvant chemotherapy, 60% of patients with AOC will relapse within 5 years. Most recurrences occur in the peritoneal cavity, suggesting the existence of occult sanctuaries where ovarian cancer cells (OCC) are protected. In murine models, surgical stress favors tumor growth; however, it has never been established that surgery may affect OCC sensitivity to subsequent chemotherapy. In this study, we investigated how the surgical stress could affect the chemosensitivity of OCC. Methods To avoid bias due to tumor burden in peritoneal cavity and duration of surgery, we used peritoneal biopsies from patients without a malignancy at precise time points. During laparotomies, peritoneal biopsies at the incision site were performed at the time of incision (H0 sample) and 1 h after initiation of surgery (H1 sample). We evaluated the chemoresistance to Taxol (0–20 µM) induced by H0 or H1 incubation (24 h) in two ovarian cancer cell lines OVCAR3 and SKOV3 and a primary cancer cell lines derived in our laboratory. Results Our results indicate that stressed peritoneum overexpressed cytokines, resulting in OCC increased resistance to therapy. Among these cytokines, IL8 was responsible for the resistance to apoptosis through the AKT pathway activation. Chemoresistance in OCC persists through the establishment of an autocrine IL8 loop. Finally, in a cohort of 32 patients, we showed an impact of IL8 tumoral overexpression on chemosensitivity and survival outcomes with a significant association to earlier recurrence. Conclusions Our study demonstrated that precision surgery where targeted treatment would be used in combination with surgery is essential to obtain better tumor control. Electronic supplementary material The online version of this article (10.1186/s12967-018-1643-z) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Jennifer Pasquier
- Stem Cell and Microenvironment Laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, PO: 24144, Doha, Qatar.,Department Genetic Medicine, Weill Cornell Medical College, New York, NY, USA.,INSERM U955, Equipe 7, Créteil, France
| | - Fabien Vidal
- Stem Cell and Microenvironment Laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, PO: 24144, Doha, Qatar.,Department Genetic Medicine, Weill Cornell Medical College, New York, NY, USA
| | - Jessica Hoarau-Véchot
- Stem Cell and Microenvironment Laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, PO: 24144, Doha, Qatar
| | - Claire Bonneau
- Service de Gynécologie Obstétrique, Hopital Tenon (Assistance Publique-Hôpitaux de Paris), 4 rue de la Chine, 75020, Paris, France
| | - Emile Daraï
- Service de Gynécologie Obstétrique, Hopital Tenon (Assistance Publique-Hôpitaux de Paris), 4 rue de la Chine, 75020, Paris, France
| | - Cyril Touboul
- Service de Gynécologie-Obstétrique et Médecine de la Reproduction, Faculté de médecine de Créteil UPEC-Paris XII, Centre Hospitalier Intercommunal de Créteil, 40 Avenue de Verdun, 94000, Créteil, France
| | - Arash Rafii
- Stem Cell and Microenvironment Laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, PO: 24144, Doha, Qatar. .,Department Genetic Medicine, Weill Cornell Medical College, New York, NY, USA. .,Service de chirurgie Gynécologique, Hôpital Foch, 92100, Suresnes, France.
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Bartolini I, Ringressi MN, Melli F, Risaliti M, Brugia M, Mini E, Batignani G, Bechi P, Boni L, Taddei A. Analysis of Prognostic Factors for Resected Synchronous and Metachronous Liver Metastases from Colorectal Cancer. Gastroenterol Res Pract 2018; 2018:5353727. [PMID: 30116264 PMCID: PMC6079496 DOI: 10.1155/2018/5353727] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2018] [Accepted: 06/19/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Surgical treatment is the cornerstone in the management of colorectal cancer (CRC) liver metastases. The aim of this study is to identify clinicopathological factors affecting disease-free (DFS) and overall survival (OS) in patients undergoing potentially curative liver resection for CRC metastasis. METHODS All consecutive patients undergoing liver resection for first recurrence of CRC from February 2006 to February 2018 were included. Prognostic impact of factors related to the patient, primary and metastatic tumors, was retrospectively tested through univariate and multivariate analyses. RESULTS Seventy patients were included in the study. Median postoperative follow-up was 37 months (range 1-119). Median DFS and OS were 15.2 and 62.7 months, and 5-year DFS and OS rates were 16% and 53%. In univariate analysis, timing of metastasis presentation/treatment (combined colorectal and liver resection, "bowel first" approach or metachronous presentation) (p < 0.0001), ASA score (p = 0.003), chemotherapy after liver surgery (p = 0.028), T stage (p = 0.021), number of resected liver lesions (p < 0.0001), and liver margin status (p = 0.032) was significantly associated with DFS while peritoneal resection at colorectal surgery (p = 0.026), ASA score (p = 0.036), extension of liver resection (p = 0.024), chemotherapy after liver surgery (p = 0.047), and positive nodes (p = 0.018) with OS. In multivariate analysis, timing of metastasis presentation/treatment, ASA score, and chemotherapy (before and after liver surgery) resulted significantly associated with DFS and timing of metastasis presentation/treatment, positive nodes, peritoneal resection at colorectal surgery, and surgical approach (open or minimally invasive) of colorectal resection with OS. CONCLUSIONS Surgery may provide good DFS and OS rates for CRC liver metastasis. Patient selection for surgery and correct timing of intervention within a multidisciplinary approach may be improved by taking into account negative prognostic factors which stress the importance of systemic therapy.
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Affiliation(s)
- Ilenia Bartolini
- Department of Surgery and Translational Medicine, University of Florence, AOU Careggi, Largo Brambilla 3, 50134 Florence, Italy
| | - Maria Novella Ringressi
- Department of Surgery and Translational Medicine, University of Florence, AOU Careggi, Largo Brambilla 3, 50134 Florence, Italy
| | - Filippo Melli
- Department of Surgery and Translational Medicine, University of Florence, AOU Careggi, Largo Brambilla 3, 50134 Florence, Italy
| | - Matteo Risaliti
- Department of Surgery and Translational Medicine, University of Florence, AOU Careggi, Largo Brambilla 3, 50134 Florence, Italy
| | - Marco Brugia
- Department of Experimental and Clinical Medicine, AOU Careggi, Largo Brambilla 3, 50134 Florence, Italy
| | - Enrico Mini
- Department of Experimental and Clinical Medicine, AOU Careggi, Largo Brambilla 3, 50134 Florence, Italy
| | - Giacomo Batignani
- Department of Surgery and Translational Medicine, University of Florence, AOU Careggi, Largo Brambilla 3, 50134 Florence, Italy
| | - Paolo Bechi
- Department of Surgery and Translational Medicine, University of Florence, AOU Careggi, Largo Brambilla 3, 50134 Florence, Italy
| | - Luca Boni
- Clinical Trials Coordinating Center of Istituto Toscano Tumori, AOU Careggi, Largo Brambilla 3, 50134 Florence, Italy
| | - Antonio Taddei
- Department of Surgery and Translational Medicine, University of Florence, AOU Careggi, Largo Brambilla 3, 50134 Florence, Italy
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