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Bjerregaard F, Asklid D, Ljungqvist O, Elliot AH, Pekkari K, Gustafsson UO. Risk factors for anastomotic leakage in colonic procedures within an ERAS-protocol. A retrospective cohort study from the Swedish part of the international ERAS-database. World J Surg 2024; 48:1749-1758. [PMID: 38719788 DOI: 10.1002/wjs.12205] [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: 12/18/2023] [Accepted: 04/23/2024] [Indexed: 07/05/2024]
Abstract
BACKGROUND Research on anastomotic leakage (AL) in colonic procedures within an Enhanced Recovery After Surgery (ERAS) protocol has not yet been conducted. The aim of this study was to identify risk factors for AL after colonic surgery. METHODS The study included all consecutively recorded patients operated with colonic resection surgery in the Swedish part of the international ERAS® Interactive Audit System (EIAS) between September 2009 and June 2022. The cohort was analyzed and evaluated regarding risk factors for AL. RESULTS Altogether 10,632 patients were included, 10,219 were without AL and 413 (3.9%) were with AL. After adjusted analysis, male sex (4.6% AL), OR: 1.49; 95% CI (1.16-1.90), obesity (4.8% AL), OR: 1.62; 95% CI (1.18-2.24), previous surgery (4.4% AL), OR: 1.45; 95% CI (1.14-1.86), open surgery (4.4% AL), OR: 1.36; 95% CI (1.02-1.83), anastomosis between small bowel and rectum (13.1% AL), OR: 3.97; 95% CI (2.23-7.10), stapled anastomosis (5.3% AL), OR: 2.46; 95% CI (1.79-3.38), inhalation anesthesia (4.2% AL), OR: 1.80; 95% CI (1.26-2.57), and conversion to open surgery (5.5% AL), OR 1.49; 95% CI (1.02-2.19) were significant risk factors for AL. Although pre and intraoperative compliance to the ERAS-protocol was similar, excess of fluids day 0 was an independent predictor for AL. CONCLUSION Male sex, obesity, previous surgery, open surgery, stapled anastomotic technique, anastomosis between small bowel and rectum, inhalation anesthesia, conversion to open surgery, and among ERAS interventions, excess of fluids day 0, were significant risk factors for AL.
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Affiliation(s)
- Felix Bjerregaard
- Department of Clinical Sciences at Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden
- Department of Surgery and Urology, Danderyd Hospital, Stockholm, Sweden
| | - Daniel Asklid
- Department of Clinical Sciences at Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden
- Department of Surgery and Urology, Danderyd Hospital, Stockholm, Sweden
| | - Olle Ljungqvist
- Department of Surgery, Örebro University and University Hospital, Örebro & Institute of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Anders H Elliot
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- Department of Pelvic Cancer, Division of Coloproctology, Center for Digestive Diseases, Karolinska University Hospital, Solna, Sweden
| | - Klas Pekkari
- Department of Clinical Sciences at Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Ulf O Gustafsson
- Department of Clinical Sciences at Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- Department of Pelvic Cancer, Division of Coloproctology, Center for Digestive Diseases, Karolinska University Hospital, Solna, Sweden
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Lee C, Park IJ. Sex Disparities in Rectal Cancer Surgery: An In-Depth Analysis of Surgical Approaches and Outcomes. World J Mens Health 2024; 42:304-320. [PMID: 38449456 PMCID: PMC10949018 DOI: 10.5534/wjmh.230335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 11/30/2023] [Accepted: 12/07/2023] [Indexed: 03/08/2024] Open
Abstract
Anatomical and physiological differences exist between sex, leading to variations in how diseases, such as rectal cancer, are prevalence and treatment outcomes of diseases including rectal cancer. In particular, in the case of rectal cancer, anatomical differences may be associated with surgical challenges, and these factors are believed to be important contributors to potential disparities in postoperative recovery, associated complications, and oncological outcomes between male and female patients. However, there is still ongoing debate regarding this matter. Significantly, the male pelvic anatomy is distinguished by its narrower dimensions, which can present surgical challenges and impede visual access during operative procedures, rendering it more complex than surgical interventions in the female pelvis. As a result, this anatomical difference leads to a greater occurrence of postoperative complications, such as anastomotic leakage. Moreover, the pelvis houses nerves that are vital for urinary and genital functions, underscoring the need to assess the potential risks of sexual and urinary dysfunction in rectal cancer surgery. These postoperative complications can significantly impact the quality of life; therefore, it is imperative to perform surgery with an understanding of the structural differences between sexes. Therefore, to address the limitations imposed by anatomical structures, new approaches such as robotic surgery, trans-anal total mesorectal excision, and intraoperative neuromonitoring are being introduced. Furthermore, it is essential to conduct research into fundamental mechanisms that may give rise to differences in surgical outcomes and oncological results between sexes. By comprehending the disparities between males and females, we can advance toward personalized treatments. Consequently, this review outlines variations in surgical approaches, complications, and treatments for rectal cancer in male and female patients.
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Affiliation(s)
- Chungyeop Lee
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - In Ja Park
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
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Garcia-Alonso I, Velasco-Oraa X, Cearra I, Iturrizaga Correcher S, Mar Medina C, Alonso-Varona A, García Ruiz de Gordejuela A, Ruiz-Montesinos I, Herrero de la Parte B. Prophylactic Treatment of Intestinal Ischemia-Reperfusion Injury Reduces Mucosal Damage and Improves Intestinal Absorption. J Inflamm Res 2023; 16:4141-4152. [PMID: 37750172 PMCID: PMC10518153 DOI: 10.2147/jir.s426396] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 09/02/2023] [Indexed: 09/27/2023] Open
Abstract
Purpose Intestinal ischemia-reperfusion injury (i-IRI) involves a blood flow interruption in an intestinal segment followed by blood flow restoration. When blood flow is restored, oxidative and inflammatory molecules are distributed throughout the bloodstream, triggering both local and systemic damage. Our goal was to evaluate the potential of three antioxidant and/or anti-inflammatory compounds (curcumin, dexmedetomidine and α-tocopherol) to prevent or reverse local and systemic damage induced by i-IRI. Methods i-IRI was induced by placing a microvascular clip in the superior mesenteric artery of female WAG/RijHsd rats; the clip was removed after 1h and reperfusion was allowed for 4h. Curcumin (200 mg/kg, orally), α-tocopherol (20 mg/kg, i.p.), and dexmedetomidine (5 or 20 µg/kg, s.c.; DEX5 and DEX20, respectively) were administered. Blood and terminal ileum specimens were collected for biochemical and histological determination. Furthermore, D-xylose absorption test was performed to evaluate intestinal absorption; after completing the 1-hour ischemia and 4-hour reperfusion period, 1 mL of aqueous D-xylose solution (0.615 mg/mL) was administered orally, and one hour later, plasma D-xylose levels were quantified. Results The histological injury degree (HID) measured by the Chiu scale was significantly reduced when the treatments were applied (non-treated rats, 2.6 ± 0.75; curcumin, 1.54 ± 0.8; DEX5, 1.47 ± 0.7; DEX20 1.14 ± 0.5; and α-tocopherol, 1.01 ± 0.6); intestinal absorptive capacity also improved in all cases healthy rats (2.06 ± 0.07 µg/mL; non-treated, 1.18 ± 0.07 µg/mL; curcumin 1.76 ± 0.3 µg/mL; DEX5, 2.29 ± 0.2 µg/mL; DEX20, 2.25 ± 0.26 µg/mL; and α-tocopherol 1.66 ± 0.21 µg/mL). However, it failed to reduce liver enzyme levels. Finally, only dexmedetomidine significantly reduced urea and creatinine levels compared to non-treated animals. Conclusion All drugs were effective in reducing HID, although α-tocopherol was effective to a greater extent. Only dexmedetomidine reverted intestinal absorption to normal values of healthy animals.
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Affiliation(s)
- Ignacio Garcia-Alonso
- Department of Surgery and Radiology and Physical Medicine, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, 48940, Spain
- Interventional Radiology Research Group, Biocruces Bizkaia Health Research Institute, Barakaldo, 48903, Spain
| | - Xabier Velasco-Oraa
- Department of Anaesthesia, Hospital Clínic of Barcelona, Barcelona, 08036, Spain
| | - Iñigo Cearra
- Department of Surgery and Radiology and Physical Medicine, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, 48940, Spain
- Department of Orthopedics, Basurto University Hospital, Osakidetza Basque Health Service, Bilbao, 48013, Spain
- Regenerative Therapies, Osteoarticular and Tendon Pathology Research Group, Biocruces Bizkaia Health Research Institute, Barakaldo, 48903, Spain
| | | | - Carmen Mar Medina
- Department of Clinical Analyses, Galdakao-Usansolo University Hospital, Galdakao, 48960, Spain
| | - Ana Alonso-Varona
- Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, 48940, Spain
| | - Amador García Ruiz de Gordejuela
- Department of Surgery and Radiology and Physical Medicine, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, 48940, Spain
- Department of Gastrointestinal Surgery, Donostia University Hospital, Osakidetza Basque Health Service, Donostia, 20014, Spain
| | - Inmaculada Ruiz-Montesinos
- Department of Surgery and Radiology and Physical Medicine, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, 48940, Spain
- Department of Gastrointestinal Surgery, Donostia University Hospital, Osakidetza Basque Health Service, Donostia, 20014, Spain
| | - Borja Herrero de la Parte
- Department of Surgery and Radiology and Physical Medicine, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, 48940, Spain
- Interventional Radiology Research Group, Biocruces Bizkaia Health Research Institute, Barakaldo, 48903, Spain
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Engel RM, Oliva K, Centauri S, Wang W, McMurrick PJ, Yap R. Impact of Anastomotic Leak on Long-term Oncological Outcomes After Restorative Surgery for Rectal Cancer: A Retrospective Cohort Study. Dis Colon Rectum 2023; 66:923-933. [PMID: 36538716 DOI: 10.1097/dcr.0000000000002454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
BACKGROUND Anastomotic leak after restorative surgery for rectal cancer is a major complication and may lead to worse long-term oncological and survival outcomes. OBJECTIVE The purpose of this study was to identify risk factors associated with anastomotic leak and to assess the perioperative and long-term oncological impact of anastomotic leak in our cohort of patients with rectal cancer. DESIGN A retrospective analysis was performed on data from the prospectively maintained Cabrini Monash colorectal neoplasia database. Patients who had undergone rectal cancer resection and subsequently received anastomosis between November 2009 and May 2020 were included in this study. Patient and tumor characteristics, technical risk factors, and short-term and perioperative as well as long-term oncological and survival outcomes were assessed. SETTINGS The study was conducted in 3 tertiary hospitals. PATIENTS A total of 693 patients met the inclusion criteria for this study. MAIN OUTCOME MEASURES Univariate analyses were performed to assess the relationship between anastomotic leak and patient and technical risk factors, as well as perioperative and long-term outcomes. Univariate and multivariate proportional HR models of overall and disease-free survival were calculated. Kaplan-Meier survival analyses assessed disease-free and overall survival. RESULTS Anastomotic leak rate was 3.75%. Males had an increased risk of anastomotic leak, as did patients with hypertension and ischemic heart disease. Patients who experience an anastomotic leak were more likely to require reoperation and hospital readmission and were more likely to experience an inpatient death. Disease-free and overall survival were also negatively impacted by anastomotic leaks. LIMITATIONS This is a retrospective analysis of data from only 3 centers with the usual limitations. However, these effects have been minimized because of the high quality and completeness of the prospective data collection. CONCLUSIONS Anastomotic leaks after restorative surgery negatively affect long-term oncological and survival outcomes for patients with rectal cancer. See Video Abstract at http://links.lww.com/DCR/C81 . IMPACTO DE LA FUGA ANASTOMTICA EN LOS RESULTADOS ONCOLGICOS A LARGO PLAZO TRAS CIRUGA RESTAURADORA PARA EL CNCER DE RECTO UN ESTUDIO DE COHORTE RETROSPECTIVO ANTECEDENTES:La fuga anastomótica tras una cirugía restauradora para el cáncer de recto es una complicación mayor y puede conducir a peores resultados oncológicos y de supervivencia a largo plazo.OBJETIVO:El propósito de este estudio fue identificar los factores de riesgo asociados con la fuga anastomótica y evaluar el impacto oncológico perioperatorio y a largo plazo de la fuga anastomótica en nuestra cohorte de pacientes con cáncer de recto.DISEÑO:Se realizó un análisis retrospectivo de datos obtenidos de la base de datos Cabrini Monash sobre neoplasia colorrectal la cual es mantenida prospectivamente. Se incluyeron en este estudio pacientes que fueron sometidos a una resección del cáncer de recto y que posteriormente recibieron una anastomosis entre noviembre de 2009 y mayo de 2020. Se evaluaron las características del paciente y del tumor, los factores de riesgo relacionados a la técnica, los resultados oncológicos y de supervivencia perioperatorio, así como los resultados a corto y largo plazo.AJUSTES:El estudio se realizó en tres hospitales terciarios.PACIENTES:Un total de 693 pacientes cumplieron con los criterios de inclusión para este estudio.PRINCIPALES MEDIDAS DE RESULTADO:Se realizaron análisis univariados para evaluar la relación entre la fuga anastomótica y aquellos factores relacionados al paciente, a la técnica, así como los resultados perioperatorios y a largo plazo. Se calcularon modelos de razón de riesgo proporcional univariante y multivariante de supervivencia global y libre de enfermedad. Los análisis de supervivencia de Kaplan-Meier evaluaron la supervivencia libre de enfermedad y la supervivencia global.RESULTADOS:La tasa de fuga anastomótica fue del 3,75%. Los hombres tenían un mayor riesgo de fuga anastomótica al igual que aquellos pacientes con hipertensión y cardiopatía isquémica. Los pacientes que sufrieron una fuga anastomótica tuvieron mayores probabilidades de requerir una reintervención y reingreso hospitalario, así como también tuvieron mayores probabilidades de sufrir una muerte hospitalaria. La supervivencia libre de enfermedad y general también se vio afectada negativamente por las fugas anastomóticas.LIMITACIONES:Este es un análisis retrospectivo de datos de solo tres centros con las limitaciones habituales. Sin embargo, estos efectos han sido minimizados debido a la alta calidad y la exhaustividad de la recopilación prospectiva de datos.CONCLUSIONES:Las fugas anastomóticas después de una cirugía restauradora afectan negativamente los resultados oncológicos y de supervivencia a largo plazo para los pacientes con cáncer de recto. Consulte Video Resumen en http://links.lww.com/DCR/C81 . (Traducción-Dr. Osvaldo Gauto ).
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Affiliation(s)
- Rebekah M Engel
- Department of Surgery, Cabrini Health, Cabrini Monash University, Malvern, Victoria, Australia
- Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia
- Stem Cells and Development Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
| | - Karen Oliva
- Department of Surgery, Cabrini Health, Cabrini Monash University, Malvern, Victoria, Australia
| | - Suellyn Centauri
- Department of Surgery, Cabrini Health, Cabrini Monash University, Malvern, Victoria, Australia
| | - Wei Wang
- Cabrini Institute, Malvern, Victoria, Australia
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia
| | - Paul J McMurrick
- Department of Surgery, Cabrini Health, Cabrini Monash University, Malvern, Victoria, Australia
| | - Raymond Yap
- Department of Surgery, Cabrini Health, Cabrini Monash University, Malvern, Victoria, Australia
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Li R, Zhou J, Zhao S, Sun Q, Wang D. Prediction model of anastomotic leakage after anterior resection for rectal cancer-based on nomogram and multivariate analysis with 1995 patients. Int J Colorectal Dis 2023; 38:139. [PMID: 37212917 DOI: 10.1007/s00384-023-04438-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/09/2023] [Indexed: 05/23/2023]
Abstract
BACKGROUND Postoperative anastomotic leakage for rectal cancer shows higher morbidity with grievous concomitant symptoms. Accurate assessment of the incidence of anastomotic leakage, multivariate analysis, and establishment of a scientific prediction model can be useful to dispose of its possible severe clinical consequences. METHODS This retrospective study collected 1995 consecutive patients who underwent anterior resection of rectal cancer with primary anastomosis at Northern Jiangsu People's Hospital between January 2016 and June 2022. Independent risk factors associated with anastomotic leakage were analyzed by univariate and multivariate logistic regression. The chosen independent risk factors were used to construct a nomogram risk prediction model whose availability was evaluated by using a bootstrapped-concordance index and calibration plots with R software. RESULTS A total of 1995 patients who underwent anterior resection for rectal cancer were included while 120 patients were diagnosed with anastomotic leakage, an incidence of 6.0%. Univariate analysis and its concomitant multivariate cox regression analysis indicated that independent risk factors associated with anastomotic leakage included male gender (odds ratio (OR) = 2.873), diabetes (OR = 2.480), neoadjuvant therapy (OR = 5.283), tumor's distance from the anus verge < 5 cm (OR = 5.824), tumor size ≥ 5 cm (OR = 4.888), and the blood lose > 50 mL (OR = 9.606).We established a nomogram prediction model with proper applicability (concordance index, 0.83) and the calibration curve to justify its predictive ability that the predicted occurrence probability keeps a high degree of consistency with the actual occurrence probability. Meanwhile, the area under the receiver operating characteristic (ROC) curve was 0.83. CONCLUSIONS The characteristics of patients and tumor surgery-related conditions can affect the incidence of anastomotic leakage. However, whether the surgical method will affect morbidity is still controversial. Our nomogram can be seen as an effective instrument to predict anastomotic leakage after anterior resection for rectal cancer precisely.
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Affiliation(s)
- Ruiqi Li
- Northern Jiangsu People's Hospital Affiliated to Medical School of Nanjing University, Yangzhou, 225001, China
| | - Jiajie Zhou
- Northern Jiangsu People's Hospital Affiliated to Medical School of Nanjing University, Yangzhou, 225001, China
| | - Shuai Zhao
- Northern Jiangsu People's Hospital Affiliated to Medical School of Nanjing University, Yangzhou, 225001, China
| | - Qiannan Sun
- Northern Jiangsu People's Hospital, Yangzhou, China
- Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou, China
| | - Daorong Wang
- Northern Jiangsu People's Hospital Affiliated to Medical School of Nanjing University, Yangzhou, 225001, China.
- Northern Jiangsu People's Hospital, Yangzhou, China.
- Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou, China.
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Predictive Factors for Anastomotic Leakage Following Colorectal Cancer Surgery: Where Are We and Where Are We Going? Curr Oncol 2023; 30:3111-3137. [PMID: 36975449 PMCID: PMC10047700 DOI: 10.3390/curroncol30030236] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 03/03/2023] [Accepted: 03/06/2023] [Indexed: 03/09/2023] Open
Abstract
Anastomotic leakage (AL) remains one of the most severe complications following colorectal cancer (CRC) surgery. Indeed, leaks that may occur after any type of intestinal anastomosis are commonly associated with a higher reoperation rate and an increased risk of postoperative morbidity and mortality. At first, our review aims to identify specific preoperative, intraoperative and perioperative factors that eventually lead to the development of anastomotic dehiscence based on the current literature. We will also investigate the role of several biomarkers in predicting the presence of ALs following colorectal surgery. Despite significant improvements in perioperative care, advances in surgical techniques, and a high index of suspicion of this complication, the incidence of AL remained stable during the last decades. Thus, gaining a better knowledge of the risk factors that influence the AL rates may help identify high-risk surgical patients requiring more intensive perioperative surveillance. Furthermore, prompt diagnosis of this severe complication may help improve patient survival. To date, several studies have identified predictive biomarkers of ALs, which are most commonly associated with the inflammatory response to colorectal surgery. Interestingly, early diagnosis and evaluation of the severity of this complication may offer a significant opportunity to guide clinical judgement and decision-making.
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Henderson S, Bhardwaj K, Perugachi V, Espinoza-Montero P, Galligan JJ, Swain GM. In Vitro Monitoring of Nitric Oxide Release in the Mouse Colon Using a Boron-Doped Diamond Microelectrode Modified with Platinum Nanoparticles and Nafion. Anal Chem 2023; 95:1027-1037. [PMID: 36524968 DOI: 10.1021/acs.analchem.2c03731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
This research reports on the preparation of a boron-doped diamond microelectrode modified with platinum nanoparticles and Nafion and its application for detecting nitric oxide (NO) in vitro in the mouse colon. Platinum nanoparticle deposition was performed potentiodynamically using a 2.0 mmol L-1 potassium hexachloroplatinate solution and cycling from -0.2 to 1.3 V vs Ag/AgCl at 0.01 V s-1 for 10 cycles. The Nafion overlayer was applied by immersion in a solution containing 2.5% (w/v) colloidal Nafion and drying overnight at 55 °C in a humid environment. The optimal microelectrode preparation conditions were chosen based on the electrode response for NO oxidation as well as rejection of nitrite (NO2-) oxidation, the main interferent in the electrochemical detection of NO in biological media. Detection figures of merit include a sensitivity of 16.7 ± 2.7 mA M-1 cm-2 (n = 3 electrodes), a detection limit of 0.5 μmol L-1 (S/N = 3), and an electrode response reproducibility of 2.5% (RSD). Electrical stimulation and continuous amperometry were used to measure NO release from myenteric ganglia in wild-type male and female mice in response to an increasing number of electrical stimuli to study nitrergic signaling in the colon. We also present preliminary data regarding the use of optogenetics to selectively stimulate nitrergic myenteric neurons using blue light stimulation with a goal of understanding how inhibitory neuromuscular signaling is involved in the myenteric plexus circuitry that controls intestinal motility.
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Affiliation(s)
- Skye Henderson
- Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, United States
| | - Kirti Bhardwaj
- Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan 48824, United States
| | - Victoria Perugachi
- Escuela Politécnica Nacional, Facultad de Ingeniería Química y Agroindustria, Quito 170143, Ecuador
| | | | - James J Galligan
- Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan 48824, United States.,The Neuroscience Program, Michigan State University, East Lansing, Michigan 48824, United States
| | - Greg M Swain
- Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, United States.,The Neuroscience Program, Michigan State University, East Lansing, Michigan 48824, United States
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Relationship between laparoscopic total gastrectomy-associated postoperative complications and gastric cancer prognosis. Updates Surg 2023; 75:149-158. [PMID: 36369627 DOI: 10.1007/s13304-022-01402-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 10/04/2022] [Indexed: 11/13/2022]
Abstract
This study aimed to investigate the incidence and prognosis of postoperative complications after laparoscopic total gastrectomy (LTG) for gastric cancer (GC). We retrospectively enrolled 411 patients who underwent curative LTG for GC at seven institutions between January 2004 and December 2018. The patients were divided into two groups, complication group (CG) and non-complication group (non-CG), depending on the presence of serious postoperative complications (Clavien-Dindo grade III [≥ CD IIIa] or higher complications). Short-term outcomes and prognoses were compared between two groups. Serious postoperative complications occurred in 65 (15.8%) patients. No significant difference was observed between the two groups in the median operative time, intraoperative blood loss, number of lymph nodes harvested, or pathological stage; however, the 5-year overall survival (OS; CG 66.4% vs. non-CG 76.8%; p = 0.001), disease-specific survival (DSS; CG 70.1% vs. non-CG 76.2%; p = 0.011), and disease-free survival (CG 70.9% vs. non-CG 80.9%; p = 0.001) were significantly different. The Cox multivariate analysis identified the serious postoperative complications as independent risk factors for 5-year OS (HR 2.143, 95% CI 1.165-3.944, p = 0.014) and DSS (HR 2.467, 95% CI 1.223-4.975, p = 0.011). A significant difference was detected in the median days until postoperative recurrence (CG 223 days vs. non-CG 469 days; p = 0.017) between the two groups. Serious postoperative complications after LTG negatively affected the GC prognosis. Efforts to decrease incidences of serious complications should be made that may help in better prognosis in patients with GC after LTG.
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Sripathi S, Khan MI, Patel N, Meda RT, Nuguru SP, Rachakonda S. Factors Contributing to Anastomotic Leakage Following Colorectal Surgery: Why, When, and Who Leaks? Cureus 2022; 14:e29964. [DOI: 10.7759/cureus.29964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/05/2022] [Indexed: 11/06/2022] Open
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Xiang S, Yang YK, Wang TY, Yang ZT, Lu Y, Liu SL. Development and validation of a nomogram to predict anastomotic leakage in colorectal cancer based on CT body composition. Front Nutr 2022; 9:974903. [PMID: 36159450 PMCID: PMC9490075 DOI: 10.3389/fnut.2022.974903] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 08/17/2022] [Indexed: 12/02/2022] Open
Abstract
Background Anastomotic leakage (AL) is one of the most serious postoperative complications. This study aimed to investigate the predictive value of preoperative body composition for AL in patients with colorectal cancer (CRC). Methods We first reviewed data from 3,681 patients who underwent radical CRC resection 2013–2021 in our hospital, and 60 patients were diagnosed with AL after surgery. We designed a nested case-control study and two controls were randomly selected for each case according to the time and position of surgery. Body composition was measured at the level of the third lumbar vertebra based on computed tomography (CT) images. The risk factors of AL were analyzed by univariate and multivariate analysis. Nomogram was built using binary regression analysis and assessed for clinical usefulness, calibration, and discrimination. Results In the multivariate analysis, gender, blood glucose, nutrition risk screening (NRS), skeletal muscle area (SMA) and visceral fat area (VFA) were independent risk factors for developing anastomotic leakage after surgery. The prognostic model had an area under the receiver operating characteristic curve of 0.848 (95% CI, 0.781–0.914). The calibration curve showed good consistency between the predicted and observed outcomes. Decision curve analysis indicated that patients with colorectal cancer can benefit from the prediction model. Conclusions The nomogram that combined with gender, blood glucose, NRS, SMA, and VFA had good predictive accuracy and reliability to AL. It may be conveniently for clinicians to predict AL preoperatively and be useful for guiding treatment decisions.
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Affiliation(s)
- Shuai Xiang
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yong-Kang Yang
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Tong-Yu Wang
- Department of Radiology, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Zhi-Tao Yang
- Department of Radiology, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yun Lu
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, China
- *Correspondence: Yun Lu
| | - Shang-Long Liu
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, China
- Shang-Long Liu
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11
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Zarnescu EC, Zarnescu NO, Costea R. Updates of Risk Factors for Anastomotic Leakage after Colorectal Surgery. Diagnostics (Basel) 2021; 11:diagnostics11122382. [PMID: 34943616 PMCID: PMC8700187 DOI: 10.3390/diagnostics11122382] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 12/06/2021] [Accepted: 12/14/2021] [Indexed: 12/13/2022] Open
Abstract
Anastomotic leakage is a potentially severe complication occurring after colorectal surgery and can lead to increased morbidity and mortality, permanent stoma formation, and cancer recurrence. Multiple risk factors for anastomotic leak have been identified, and these can allow for better prevention and an earlier diagnosis of this significant complication. There are nonmodifiable factors such as male gender, comorbidities and distance of tumor from anal verge, and modifiable risk factors, including smoking and alcohol consumption, obesity, preoperative radiotherapy and preoperative use of steroids or non-steroidal anti-inflammatory drugs. Perioperative blood transfusion was shown to be an important risk factor for anastomotic failure. Recent studies on the laparoscopic approach in colorectal surgery found no statistical difference in anastomotic leakage rate compared with open surgery. A diverting stoma at the time of primary surgery does not appear to reduce the leak rate but may reduce its clinical consequences and the need for additional surgery if anastomotic leakage does occur. It is still debatable if preoperative bowel preparation should be used, especially for left colon and rectal resections, but studies have shown similar incidence of postoperative leak rate.
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Affiliation(s)
- Eugenia Claudia Zarnescu
- Department of General Surgery, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (E.C.Z.); (R.C.)
- Second Department of Surgery, University Emergency Hospital Bucharest, 050098 Bucharest, Romania
| | - Narcis Octavian Zarnescu
- Department of General Surgery, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (E.C.Z.); (R.C.)
- Second Department of Surgery, University Emergency Hospital Bucharest, 050098 Bucharest, Romania
- Correspondence: ; Tel.: +40-723-592-483
| | - Radu Costea
- Department of General Surgery, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (E.C.Z.); (R.C.)
- Second Department of Surgery, University Emergency Hospital Bucharest, 050098 Bucharest, Romania
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12
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Arron MNN, Greijdanus NG, ten Broek RPG, Dekker JWT, van Workum F, van Goor H, Tanis PJ, de Wilt JHW. Trends in risk factors of anastomotic leakage after colorectal cancer surgery (2011-2019): A Dutch population-based study. Colorectal Dis 2021; 23:3251-3261. [PMID: 34536987 PMCID: PMC9293104 DOI: 10.1111/codi.15911] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 08/27/2021] [Accepted: 09/07/2021] [Indexed: 01/04/2023]
Abstract
AIM Anastomotic leakage (AL) after colon cancer (CC) and rectal cancer (RC) surgery often requires reintervention. Prevalence and morbidity may change over time with evolutions in treatment strategies and changes in patient characteristics. This nationwide study aimed to evaluate changes in the incidence, risk factors and mortality from AL during the past nine years. METHODS Data of CC and RC resections with primary anastomosis were extracted from the Dutch Colorectal Audit (2011-2019). AL was registered if requiring reintervention. Three consecutive cohorts were compared using logistic regression analysis. RESULTS Incidence of AL after CC surgery decreased from 6.6% in 2011-2013 to 4.8% in 2017-2019 and increased from 8.6% to 11.9% after RC surgery. In 2011-2013, male sex, ASA ≥3, (y)pT3-4, neoadjuvant therapy, emergency surgery and multivisceral resection were identified as risk factors for AL after CC surgery. In 2017-2019, only male sex and ASA ≥3 were risk factors for AL. For RC patients, male sex and neoadjuvant therapy were a risk factor for AL in 2011-2013. In 2017-2019, transanal approach was also a risk factor for AL. Postoperative mortality rate after AL was 12% (CC) and 2% (RC) in 2017-2019, without significant changes over time. CONCLUSION Contradictory trends in incidence and mortality for AL were observed among CC and RC surgery with changing risk factors over the past 9 years. High mortality after AL is only observed after CC surgery and remains unchanged. Continued efforts should be made to improve early detection and treatment of AL for these patients.
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Affiliation(s)
- Melissa N. N. Arron
- Radboud Institute for Health SciencesDepartment of SurgeryRadboud University Medical CentreNijmegenThe Netherlands
| | - Nynke G. Greijdanus
- Radboud Institute for Health SciencesDepartment of SurgeryRadboud University Medical CentreNijmegenThe Netherlands
| | - Richard P. G. ten Broek
- Radboud Institute for Health SciencesDepartment of SurgeryRadboud University Medical CentreNijmegenThe Netherlands
| | | | - Frans van Workum
- Department of SurgeryCanisius‐Wilhelmina HospitalNijmegenThe Netherlands
| | - Harry van Goor
- Radboud Institute for Health SciencesDepartment of SurgeryRadboud University Medical CentreNijmegenThe Netherlands
| | - Pieter J. Tanis
- Amsterdam UMCDepartment of SurgeryCancer Centre AmsterdamUniversity of AmsterdamAmsterdamThe Netherlands
| | - Johannes H. W. de Wilt
- Radboud Institute for Health SciencesDepartment of SurgeryRadboud University Medical CentreNijmegenThe Netherlands
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13
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Dean AE, Reichardt F, Anakk S. Sex differences feed into nuclear receptor signaling along the digestive tract. Biochim Biophys Acta Mol Basis Dis 2021; 1867:166211. [PMID: 34273530 DOI: 10.1016/j.bbadis.2021.166211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 06/14/2021] [Accepted: 07/05/2021] [Indexed: 02/07/2023]
Abstract
Sex differences in physiology are noted in clinical and animal studies. However, mechanisms underlying these observed differences between males and females remain elusive. Nuclear receptors control a wide range of physiological pathways and are expressed in the gastrointestinal tract, including the mouth, stomach, liver and intestine. We investigated the literature pertaining to ER, AR, FXR, and PPAR regulation and highlight the sex differences in nutrient metabolism along the digestive system. We chose these nuclear receptors based on their metabolic functions, and hormonal actions. Intriguingly, we noted an overlap in target genes of ER and FXR that modulate mucosal integrity and GLP-1 secretion, whereas overlap in target genes of PPARα with ER and AR modulate lipid metabolism. Sex differences were seen not only in the basal expression of nuclear receptors, but also in activation as their endogenous ligand concentrations fluctuate depending on nutrient availability. Finally, in this review, we speculate that interactions between the nuclear receptors may influence overall metabolic decisions in the gastrointestinal tract in a sex-specific manner.
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Affiliation(s)
- Angela E Dean
- Division of Nutritional Sciences, University of Illinois Urbana Champaign, Urbana, IL, United States of America
| | - François Reichardt
- Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL, United States of America
| | - Sayeepriyadarshini Anakk
- Division of Nutritional Sciences, University of Illinois Urbana Champaign, Urbana, IL, United States of America; Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL, United States of America; Cancer center at Illinois, University of Illinois at Urbana-Champaign, Urbana, IL, United States of America.
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14
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Olaiya B, Renelus BD, Filon M, Saha S. Trends in Morbidity and Mortality Following Colectomy Among Patients with Ulcerative Colitis in the Biologic Era (2002-2013): A Study Using the National Inpatient Sample. Dig Dis Sci 2021; 66:2032-2041. [PMID: 32676826 DOI: 10.1007/s10620-020-06474-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Accepted: 07/04/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Total abdominal colectomy (TAC) is a treatment modality of last recourse for patients with severe and/or refractory ulcerative colitis (UC). The goal of this study is to evaluate temporal trends and treatment outcomes following TAC among hospitalized UC patients in the biologic era. METHODS We queried the National Inpatient Sample (NIS) to identify patients older than 18 years with a primary diagnosis of ulcerative colitis (UC) who underwent TAC between 2002 and 2013. We evaluated postoperative morbidity and mortality as outcomes of interest. Logistic regression was used to explore factors associated with postoperative morbidity and mortality after TAC. RESULTS A weighted total of 307,799 UC hospitalizations were identified. Of these, 27,853 (9%) resulted in TAC. Between 2002 and 2013, hospitalizations for UC increased by over 70%; however, TAC rates dropped significantly from 111.1 to 77.1 colectomies per 1000 UC admissions. Overall, 2.2% of patients died after TAC. Mortality rates after TAC decreased from 3.5% in 2002 to 1.4% in 2013. Conversely, morbidity rates were stable throughout the study period. UC patients with emergent admissions, higher comorbidity scores and who had TAC in low volume colectomy hospitals had poorer outcomes. Regardless of admission type, outcomes were worse if TAC was performed more than 24 h after admission. CONCLUSIONS Despite increased hospitalizations for UC, rates of TAC have declined during the post-biologic era. For UC patients who undergo TAC, mortality has declined significantly while morbidity remains stable. Older age, race, emergent admissions and delayed surgery are predictive factors of both postoperative morbidity and mortality.
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Affiliation(s)
- Babatunde Olaiya
- Department of Internal Medicine, Marshfield Clinic, Marshfield, WI, USA.
| | - Benjamin D Renelus
- Department of Gastroenterology, Brooklyn Methodist, New York-Presbyterian Hospital, Brooklyn, NY, USA
| | - Mikolaj Filon
- School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
| | - Sumona Saha
- Division of Gastroenterology and Hepatology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
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15
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Gray M, Marland JRK, Murray AF, Argyle DJ, Potter MA. Predictive and Diagnostic Biomarkers of Anastomotic Leakage: A Precision Medicine Approach for Colorectal Cancer Patients. J Pers Med 2021; 11:471. [PMID: 34070593 PMCID: PMC8229046 DOI: 10.3390/jpm11060471] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 05/19/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
Development of an anastomotic leak (AL) following intestinal surgery for the treatment of colorectal cancers is a life-threatening complication. Failure of the anastomosis to heal correctly can lead to contamination of the abdomen with intestinal contents and the development of peritonitis. The additional care that these patients require is associated with longer hospitalisation stays and increased economic costs. Patients also have higher morbidity and mortality rates and poorer oncological prognosis. Unfortunately, current practices for AL diagnosis are non-specific, which may delay diagnosis and have a negative impact on patient outcome. To overcome these issues, research is continuing to identify AL diagnostic or predictive biomarkers. In this review, we highlight promising candidate biomarkers including ischaemic metabolites, inflammatory markers and bacteria. Although research has focused on the use of blood or peritoneal fluid samples, we describe the use of implantable medical devices that have been designed to measure biomarkers in peri-anastomotic tissue. Biomarkers that can be used in conjunction with clinical status, routine haematological and biochemical analysis and imaging have the potential to help to deliver a precision medicine package that could significantly enhance a patient's post-operative care and improve outcomes. Although no AL biomarker has yet been validated in large-scale clinical trials, there is confidence that personalised medicine, through biomarker analysis, could be realised for colorectal cancer intestinal resection and anastomosis patients in the years to come.
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Affiliation(s)
- Mark Gray
- The Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush, Roslin, Midlothian, Edinburgh EH25 9RG, UK;
| | - Jamie R. K. Marland
- School of Engineering, Institute for Integrated Micro and Nano Systems, University of Edinburgh, Scottish Microelectronics Centre, King’s Buildings, Edinburgh EH9 3FF, UK;
| | - Alan F. Murray
- School of Engineering, Institute for Bioengineering, University of Edinburgh, Faraday Building, The King’s Buildings, Edinburgh EH9 3DW, UK;
| | - David J. Argyle
- The Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush, Roslin, Midlothian, Edinburgh EH25 9RG, UK;
| | - Mark A. Potter
- Department of Surgery, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK;
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16
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Risk Factors for Anastomotic Leakage in Patients with Rectal Tumors Undergoing Anterior Resection within an ERAS Protocol: Results from the Swedish ERAS Database. World J Surg 2021; 45:1630-1641. [PMID: 33733700 PMCID: PMC8093169 DOI: 10.1007/s00268-021-06054-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/26/2021] [Indexed: 01/16/2023]
Abstract
Background Research on risk factors for anastomotic leakage (AL) alone within an Enhanced Recovery After Surgery (ERAS) protocol has not yet been conducted. The aim of this study was to identify risk factors for AL and study short-term outcome after AL in patients operated with anterior resection (AR). Methods All prospectively and consecutively recorded patients operated with AR in the Swedish part of the international ERAS® Interactive Audit System (EIAS) between January 2010 and February 2020 were included. The cohort was evaluated regarding risk factors for AL and short-term outcomes, including uni- and multivariate analysis. Pre-, intra- and postoperative compliance to ERAS®Society guidelines was calculated and evaluated. Results Altogether 1900 patients were included, 155 (8.2%) with AL and 1745 without AL. Male gender, obesity, peritoneal contamination, year of surgery 2016–2020, duration of primary surgery and age remained significant predictors for AL in multivariate analysis. There was no significant difference in overall pre- and intraoperative compliance to ERAS®Society guidelines between groups. Only preadmission patient education remained as a significant ERAS variable associated with less AL. AL was associated with longer length of stay (LOS), higher morbidity rate and higher rate of reoperations. Conclusion Male gender, obesity, peritoneal contamination, duration of surgery, surgery later in study period, age and preadmission patient education were associated with AL in patients operated on with AR. Overall pre- and intraoperative compliance to the ERAS protocol was high in both groups and not associated with AL.
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17
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Kryzauskas M, Bausys A, Degutyte AE, Abeciunas V, Poskus E, Bausys R, Dulskas A, Strupas K, Poskus T. Risk factors for anastomotic leakage and its impact on long-term survival in left-sided colorectal cancer surgery. World J Surg Oncol 2020; 18:205. [PMID: 32795348 PMCID: PMC7427291 DOI: 10.1186/s12957-020-01968-8] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Accepted: 07/23/2020] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Anastomotic leakage (AL) significantly impairs short-term outcomes. The impact on the long-term outcomes remains unclear. This study aimed to identify the risk factors for AL and the impact on long-term survival in patients with left-sided colorectal cancer. METHODS Nine-hundred patients with left-sided colorectal carcinoma who underwent sigmoid or rectal resection were enrolled in the study. Risk factors for AL after sigmoid or rectal resection were identified, and long-term outcomes of patients with and without AL were compared. RESULTS AL rates following sigmoid and rectal resection were 5.1% and 10.7%, respectively. Higher ASA score (III-IV; OR = 10.54, p = 0.007) was associated with AL in patients undergoing sigmoid surgery on multivariable analysis. Male sex (OR = 2.40, p = 0.004), CCI score > 5 (OR = 1.72, p = 0.025), and T3/T4 stage tumors (OR = 2.25, p = 0.017) were risk factors for AL after rectal resection on multivariable analysis. AL impaired disease-free and overall survival in patients undergoing sigmoid (p = 0.009 and p = 0.001) and rectal (p = 0.003 and p = 0.014) surgery. CONCLUSION ASA score of III-IV is an independent risk factor for AL after sigmoid surgery, and male sex, higher CCI score, and advanced T stage are risk factors for AL after rectal surgery. AL impairs the long-term survival in patients undergoing left-sided colorectal surgery.
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Affiliation(s)
- Marius Kryzauskas
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Augustinas Bausys
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | | | - Vilius Abeciunas
- Faculty of Medicine, Vilnius University, Ciurlionio str. 21, 03101, Vilnius, Lithuania.
| | - Eligijus Poskus
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Rimantas Bausys
- Faculty of Medicine, Vilnius University, Ciurlionio str. 21, 03101, Vilnius, Lithuania
| | - Audrius Dulskas
- Faculty of Medicine, Vilnius University, Ciurlionio str. 21, 03101, Vilnius, Lithuania
| | - Kestutis Strupas
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Tomas Poskus
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
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18
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Denning NL, Aziz M, Ochani M, Prince JM, Wang P. Inhibition of a triggering receptor expressed on myeloid cells-1 (TREM-1) with an extracellular cold-inducible RNA-binding protein (eCIRP)-derived peptide protects mice from intestinal ischemia-reperfusion injury. Surgery 2020; 168:478-485. [PMID: 32439208 DOI: 10.1016/j.surg.2020.04.010] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 03/31/2020] [Accepted: 04/02/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Intestinal ischemia-reperfusion injury results in morbidity and mortality from both local injury and systemic inflammation and acute lung injury. Extracellular cold-inducible RNA-binding protein is a damage associated molecular pattern that fuels systemic inflammation and potentiates acute lung injury. We recently discovered a triggering receptor expressed on myeloid cells-1 serves as a novel receptor for extracellular cold-inducible RNA-binding protein. We developed a 7-aa peptide, named M3, derived from the cold-inducible RNA-binding protein, which interferes with cold-inducible RNA-binding protein's binding to a triggering receptor expressed on myeloid cells-1. Here, we hypothesized that M3 protects mice against intestinal ischemia-reperfusion injury. METHODS Intestinal ischemia was induced in C57BL/6 mice via clamping of the superior mesenteric artery for 60 minutes. At reperfusion, mice were treated intraperitoneally with M3 (10 mg/kg body weight) or normal saline vehicle. Mice were killed 4 hours after reperfusion and blood and lungs were collected for various analysis. A 24-hours survival after intestinal ischemia-reperfusion was assessed. RESULTS Serum levels of organ injury markers aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and lactate were increased with intestinal ischemia-reperfusion, while treatment with M3 significantly decreased their levels. Serum, intestinal, and lung levels of proinflammatory cytokines and chemokines were also increased by intestinal ischemia-reperfusion, and treatment with M3 significantly reduced these values. Intestinal ischemia-reperfusion caused significant histological intestinal and lung injuries, which were mitigated by M3. Treatment with M3 improved the survival from 40% to 80% after intestinal ischemia-reperfusion. CONCLUSION Inhibition of triggering receptor expressed on myeloid cells-1 by an extracellular cold-inducible RNA-binding protein-derived small peptide (M3) decreased inflammation, reduced lung injury, and improved survival in intestinal ischemia-reperfusion injury. Thus, blocking the extracellular cold-inducible RNA-binding protein-triggering receptor expressed on myeloid cells-1 interaction is a promising therapeutic avenue for mitigating intestinal ischemia-reperfusion injury.
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Affiliation(s)
- Naomi-Liza Denning
- Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY; Department of Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY; Elmezzi Graduate School of Molecular Medicine, Manhasset, NY
| | - Monowar Aziz
- Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY; Elmezzi Graduate School of Molecular Medicine, Manhasset, NY
| | - Mahendar Ochani
- Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY
| | - Jose M Prince
- Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY; Department of Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY; Cohen Children's Medical Center at Hofstra/Northwell Health, New Hyde Park, NY
| | - Ping Wang
- Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY; Department of Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY; Elmezzi Graduate School of Molecular Medicine, Manhasset, NY.
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19
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Wiseman JT, Kimbrough C, Beal EW, Zaidi MY, Staley CA, Grotz T, Leiting J, Fournier K, Lee AJ, Dineen S, Powers B, Veerapong J, Baumgartner JM, Clarke C, Patel SH, Dhar V, Hendrix RJ, Lambert L, Abbott DE, Pokrzywa C, Raoof M, Lee B, Fackche N, Greer J, Pawlik TM, Abdel-Misih S, Cloyd JM. Predictors of Anastomotic Failure After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Does Technique Matter? Ann Surg Oncol 2020; 27:783-792. [PMID: 31659645 DOI: 10.1245/s10434-019-07964-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Indexed: 08/30/2023]
Abstract
BACKGROUND Anastomotic failure (AF) after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) remains a dreaded complication. Whether specific factors, including anastomotic technique, are associated with AF is poorly understood. METHODS Patients who underwent CRS-HIPEC including at least one bowel resection between 2000 and 2017 from 12 academic institutions were reviewed to determine factors associated with AF (anastomotic leak or enteric fistula). RESULTS Among 1020 patients who met the inclusion criteria, the median age was 55 years, 43.9% were male, and the most common histology was appendiceal neoplasm (62.3%). The median Peritoneal Cancer Index was 14, and 93.2% of the patients underwent CC0/1 resection. Overall, 82 of the patients (8%) experienced an AF, whereas 938 (92.0%) did not. In the multivariable analysis, the factors associated with AF included male gender (odds ratio [OR], 2.2; p < 0.01), left-sided colorectal resection (OR 10.0; p = 0.03), and preoperative albumin (OR 1.8 per g/dL; p = 0.02).Technical factors such as method (stapled vs hand-sewn), timing of anastomosis, and chemotherapy regimen used were not associated with AF (all p > 0.05). Anastomotic failure was associated with longer hospital stay (23 vs 10 days; p < 0.01), higher complication rate (90% vs 59%; p < 0.01), higher reoperation rate (41% vs 9%; p < 0.01), more 30-day readmissions (59% vs 22%; p < 0.01), greater 30-day mortality (9% vs 1%; p < 0.01), and greater 90-day mortality (16% vs 8%; p = 0.02) as well as shorter median overall survival (25.6 vs 66.0 months; p < 0.01). CONCLUSIONS Among patients undergoing CRS-HIPEC, AF is independently associated with postoperative morbidity and worse long-term outcomes. Because patient- and tumor-related, but not technical, factors are associated with AF, operative technique may be individualized based on patient considerations and surgeon preference.
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MESH Headings
- Aged
- Anastomosis, Surgical/adverse effects
- Anastomosis, Surgical/mortality
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Chemotherapy, Adjuvant/adverse effects
- Chemotherapy, Adjuvant/mortality
- Chemotherapy, Cancer, Regional Perfusion/adverse effects
- Chemotherapy, Cancer, Regional Perfusion/mortality
- Combined Modality Therapy
- Cytoreduction Surgical Procedures/adverse effects
- Cytoreduction Surgical Procedures/mortality
- Female
- Follow-Up Studies
- Humans
- Hyperthermia, Induced/adverse effects
- Hyperthermia, Induced/mortality
- Male
- Neoplasms/mortality
- Neoplasms/pathology
- Neoplasms/therapy
- Prognosis
- Retrospective Studies
- Survival Rate
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Affiliation(s)
- Jason T Wiseman
- Department of Surgery, The Ohio State University, Columbus, OH, USA
| | | | - Eliza W Beal
- Department of Surgery, The Ohio State University, Columbus, OH, USA
| | | | | | - Travis Grotz
- Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | | | - Keith Fournier
- Department of Surgery, MD Anderson Cancer Center, Houston, TX, USA
| | - Andrew J Lee
- Department of Surgery, MD Anderson Cancer Center, Houston, TX, USA
| | - Sean Dineen
- Department of Surgery, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | - Benjamin Powers
- Department of Surgery, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | - Jula Veerapong
- Department of Surgery, University of California, San Diego, San Diego, CA, USA
| | - Joel M Baumgartner
- Department of Surgery, University of California, San Diego, San Diego, CA, USA
| | - Callisia Clarke
- Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Sameer H Patel
- Department of Surgery, University of Cincinnati Medical Center, Cincinnati, OH, USA
| | - Vikrom Dhar
- Department of Surgery, University of Cincinnati Medical Center, Cincinnati, OH, USA
| | - Ryan J Hendrix
- Department of Surgery, University of Massachusetts Medical School, Worcester, MA, USA
| | - Laura Lambert
- Department of Surgery, Huntsman Cancer Institute, Salt Lake City, UT, USA
| | - Daniel E Abbott
- Department of Surgery, University of Wisconsin Hospital and Clinics, Madison, WI, USA
| | - Courtney Pokrzywa
- Department of Surgery, University of Wisconsin Hospital and Clinics, Madison, WI, USA
| | - Mustafa Raoof
- Department of Surgery, City of Hope Cancer Center, Duarte, CA, USA
| | - Byrne Lee
- Department of Surgery, City of Hope Cancer Center, Duarte, CA, USA
| | - Nadege Fackche
- Department of Surgery, Johns Hopkins University, Baltimore, MD, USA
| | - Jonathan Greer
- Department of Surgery, Johns Hopkins University, Baltimore, MD, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University, Columbus, OH, USA
| | | | - Jordan M Cloyd
- Department of Surgery, The Ohio State University, Columbus, OH, USA.
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20
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Colldén H, Landin A, Wallenius V, Elebring E, Fändriks L, Nilsson ME, Ryberg H, Poutanen M, Sjögren K, Vandenput L, Ohlsson C. The gut microbiota is a major regulator of androgen metabolism in intestinal contents. Am J Physiol Endocrinol Metab 2019; 317:E1182-E1192. [PMID: 31689143 PMCID: PMC6962501 DOI: 10.1152/ajpendo.00338.2019] [Citation(s) in RCA: 138] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Androgens exert important effects both in androgen-responsive tissues and in the intestinal tract. To determine the impact of the gut microbiota (GM) on intestinal androgen metabolism, we measured unconjugated (free) and glucuronidated androgen levels in intestinal contents from the small intestine, with a low bacterial density, and from cecum and colon, with a high bacterial density. Using a specific, sensitive gas chromatography-tandem mass spectrometry method, we detected high levels of glucuronidated testosterone (T) and dihydrotestosterone (DHT) in small intestinal content of mice of both sexes, whereas in the distal intestine we observed remarkably high levels of free DHT, exceeding serum levels by >20-fold. Similarly, in young adult men high levels of unconjugated DHT, >70-fold higher than in serum, were detected in feces. In contrast to mice with a normal GM composition, germ-free mice had high levels of glucuronidated T and DHT, but very low free DHT levels, in the distal intestine. These findings demonstrate that the GM is involved in intestinal metabolism and deglucuronidation of DHT and T, resulting in extremely high free levels of the most potent androgen, DHT, in the colonic content of young and healthy mice and men.
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Affiliation(s)
- Hannah Colldén
- Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Andreas Landin
- Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Ville Wallenius
- Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Erik Elebring
- Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Lars Fändriks
- Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Maria E Nilsson
- Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Henrik Ryberg
- Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Matti Poutanen
- Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology and Turku Center for Disease Modeling, University of Turku, Turku, Finland
| | - Klara Sjögren
- Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Liesbeth Vandenput
- Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Claes Ohlsson
- Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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Tapper J, Arver S, Holm T, Bottai M, Machado M, Jasuja R, Martling A, Buchli C. Acute primary testicular failure due to radiotherapy increases risk of severe postoperative adverse events in rectal cancer patients. Eur J Surg Oncol 2019; 46:98-104. [PMID: 31350073 DOI: 10.1016/j.ejso.2019.07.023] [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: 05/08/2019] [Revised: 07/15/2019] [Accepted: 07/18/2019] [Indexed: 02/03/2023] Open
Abstract
AIM The aim of this study is to analyze postoperative adverse events (AE) in relation to acute primary testicular failure after radiotherapy (RT) for rectal cancer. METHOD This relation was assessed in 104 men, included in a previous prospective cohort study of men treated with surgical resection of the rectum for rectal cancer stage I-III. Postoperative AE were graded according to Clavien-Dindo (2004). Grade 3 or more was set as cut-off for severe postoperative AE. The impact of primary testicular failure on postoperative AE was related to the cumulative mean testicular dose (TD) and the change in Testosterone (T) and Luteinizing hormone (LH) sampled at baseline and after RT. RESULTS Twenty-six study participants (25%) had severe postoperative AE. Baseline characteristics and endocrine testicular function did not differ significantly between groups with (AE+) and without severe postoperative AE (AE-). After RT, the LH/T-ratio was higher in AE+, 0.603 (0.2-2.5) vs 0.452 (0.127-5.926) (p = 0.035). The longitudinal regression analysis showed that preoperative change in T (OR 0.844, 95% CI 0.720-0.990, p = 0.034), LH/T-ratio (OR 2.020, 95% CI 1.010-4.039, p = 0.047) and low T (<8 nmol/L, OR 2.605, 95 CI 0.951-7.139, p = 0.063) were related to severe postoperative AE. CONCLUSION Preoperative decline in T due to primary testicular failure induced by preoperative RT could be a risk factor regarding short-term outcome of surgery in men with rectal cancer.
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Affiliation(s)
- John Tapper
- Department of Molecular Medicine and Surgery, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden.
| | - Stefan Arver
- Department of Medicine/Huddinge Karolinska Institutet and ANOVA, Karolinska University Hospital, Stockholm, Sweden
| | - Torbjörn Holm
- Department of Molecular Medicine and Surgery, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden
| | - Matteo Bottai
- Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | | | - Ravi Jasuja
- Function Promoting Therapies, Waltham, MA, USA; Research Program in Men's Health: Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Anna Martling
- Department of Molecular Medicine and Surgery, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden
| | - Christian Buchli
- Department of Molecular Medicine and Surgery, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden
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22
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Arezzo A, Migliore M, Chiaro P, Arolfo S, Filippini C, Di Cuonzo D, Cirocchi R, Morino M. The REAL (REctal Anastomotic Leak) score for prediction of anastomotic leak after rectal cancer surgery. Tech Coloproctol 2019; 23:649-663. [PMID: 31240416 DOI: 10.1007/s10151-019-02028-4] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Accepted: 06/20/2019] [Indexed: 12/31/2022]
Abstract
BACKGROUND Anastomotic leak after rectal cancer surgery is a severe complication associated with poorer oncologic outcome and quality of life. Preoperative assessment of the risk for anastomotic leak is a key component of surgical planning, including the opportunity to create a defunctioning stoma. OBJECTIVE The purpose of this study was to identify and quantify the risk factors for anastomotic leak to minimize risk by either not restoring bowel continuity or protecting the anastomosis with a temporary diverting stoma. METHODS Potentially relevant studies were identified from the following databases: PubMed, Embase and Cochrane Library. This meta-analysis included studies on transabdominal resection for rectal cancer that reported data about anastomotic leak. The risk for anastomotic leak after rectal cancer surgery was investigated. Preoperative, intraoperative, and postoperative factors were extracted and used to compare anastomotic leak rates. All variables demonstrating a p value < 0.1 in the univariate analysis were entered into a multivariate logistic regression model to determine the risk factors for anastomotic leak. RESULTS Twenty-six centers provided individual data on 9735 patients. Selected preoperative covariates (time before surgery, age, gender, smoking, previous abdominal surgery, BMI, diabetes, ASA, hemoglobin level, TNM classification stage, anastomotic distance) were used as independent factors in a logistic regression model with anastomotic leak as dependent variable. With a threshold value of the receiver operating characteristics (ROC) curve corresponding to 0.0791 in the training set, the area under the ROC curve (AUC) was 0.585 (p < 0.0001). Sensitivity and specificity of the model's probability > 0.0791 to identify anastomotic leak were 79.1% and 32.9%, respectively. Accuracy of the threshold value was confirmed in the validation set with 77.8% sensitivity and 35.2% specificity. CONCLUSIONS We trust that, with further refinement using prospective data, this nomogram based on preoperative risk factors may assist surgeons in decision making. The score is now available online ( http://www.real-score.org ).
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Affiliation(s)
- A Arezzo
- Department of Surgical Sciences, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy.
| | - M Migliore
- Department of Surgical Sciences, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy
| | - P Chiaro
- Department of Surgical Sciences, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy
| | - S Arolfo
- Department of Surgical Sciences, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy
| | - C Filippini
- Department of Surgical Sciences, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy
| | - D Di Cuonzo
- Cancer Epidemiology Unit, San Giovanni Battista Hospital, CPO Piemonte, University of Turin, Turin, Italy
| | - R Cirocchi
- Department of General Surgery, Terni Hospital, University of Perugia, Terni, Italy
| | - M Morino
- Department of Surgical Sciences, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy
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23
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Jiang HH, Dong XL, Tang X, Li AJ, Chang Y, Li HG, Chen Y, Zhang ZY, Tang EJ, Lin MB. Nomogram for Predicting Risk of Intestinal Complications After Colorectal Cancer Surgery. Med Sci Monit 2019; 25:2104-2111. [PMID: 30897070 PMCID: PMC6439933 DOI: 10.12659/msm.915692] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Background Intestinal complications are a major cause of morbidity after colorectal cancer surgery. This study aimed to develop an effective nomogram for predicting risk of intestinal complications following colorectal cancer surgery. Material/Methods We retrospectively analyzed 1876 patients who underwent colorectal cancer surgery at Yangpu and Zhuji hospitals from January 2013 to October 2018. Intestinal complications were defined as intestinal obstruction, leakage or bleeding, or peritonitis within 30 days after surgery. A logistic regression model was used to identify the risk factors associated with postoperative intestinal complications, and a nomogram for intestinal complications was established. The predictive accuracy of the nomogram was assessed using area under the receiver operating characteristic curve (AUC) and calibration plot. Results A total of 164 patients (8.7%) developed intestinal complications after colorectal cancer surgery; 35 (21.3%) of whom died in the postoperative period. Multivariate logistic analysis showed that male gender, history of abdominal surgery, preoperative intestinal obstruction/perforation, metastatic cancer, and lower level of hemoglobin and prognostic nutrition index were independent risk factors (P<0.05 for all). A nomogram was then constructed, and it displayed good accuracy in predicting postoperative intestinal complications with an AUC of 0.76. The calibration plot also showed an excellent agreement between the predicted and observed probabilities. Conclusions We constructed a nomogram based on clinical variables, which could provide individual prediction of postoperative intestinal complications with good accuracy.
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Affiliation(s)
- Hui-Hong Jiang
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China (mainland).,Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai, China (mainland)
| | - Xian-Long Dong
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China (mainland).,Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai, China (mainland)
| | - Xuan Tang
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China (mainland).,Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai, China (mainland)
| | - A-Jian Li
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China (mainland).,Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai, China (mainland)
| | - Yi Chang
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China (mainland)
| | - Hua-Guang Li
- Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai, China (mainland).,Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China (mainland)
| | - Ying Chen
- Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai, China (mainland).,Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China (mainland)
| | - Zhi-Yong Zhang
- Department of General Surgery, Zhuji People's Hospital of Zhejiang Province, Zhuji, Zhejiang, China (mainland)
| | - Er-Jiang Tang
- Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai, China (mainland).,Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China (mainland)
| | - Mou-Bin Lin
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China (mainland).,Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai, China (mainland)
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Females Are More Resistant to Ischemia-Reperfusion-induced Intestinal Injury Than Males. Ann Surg 2019; 272:1070-1079. [PMID: 30614877 DOI: 10.1097/sla.0000000000003167] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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25
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der Hagopian O, Dahlberg M, Heinius G, Nordberg J, Gustafsson J, Nordenvall C, Sandblom G, Farahnak P, Everhov ÅH. Perirenal fat surface area as a risk factor for perioperative difficulties and 30-day postoperative complications in elective colon cancer surgery. Colorectal Dis 2018; 20:1078-1087. [PMID: 29956867 DOI: 10.1111/codi.14322] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Accepted: 06/21/2018] [Indexed: 02/08/2023]
Abstract
AIM Visceral obesity is associated with perioperative and postoperative complications in colorectal surgery. We aimed to investigate the association between the perirenal fat surface area (PRF) and postoperative complications. METHOD Data on 610 patients undergoing curative, elective colon cancer resection between 2006 and 2016 at Stockholm South General Hospital were retrieved from a local quality register. We assessed perioperative and postoperative outcomes using a multinomial regression model adjusted for age, sex, American Society of Anesthesiologists classification and surgical approach (open/laparoscopy) in relation to PRF. RESULTS PRF could be measured in 605 patients; the median area was 24 cm2 . Patients with PRF ≥ 40 cm2 had longer operation time (median 223 vs 184 min), more intra-operative bleeding (250 vs 125 ml), reoperations (11% vs 6%), surgical complications (27% vs 13%) and nonsurgical infectious complications (16% vs 9%) than patients with PRF < 40 cm2 , but there were no differences in the need for intensive care or duration of hospital stay. The multivariate analyses revealed an increased risk of any complication [OR 1.68 (95% CI 1.1-2.6)], which was even more pronounced for moderate complications [Clavien-Dindo II, OR 2.14 (CI 1.2-2.4]; Clavien-Dindo III, OR 2.35 (CI 1.0-5.5)] in patients with PRF ≥ 40 vs < 40 cm2 . The absolute risk of complications was similar in men and women with PRF ≥ 40 cm2 . CONCLUSION PRF, an easily measured indirect marker of visceral obesity, was associated with overall and moderate complications in men and women and could serve as a useful tool in the assessment of preoperative risk.
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Affiliation(s)
- O der Hagopian
- Department of Clinical Science and Education Södersjukhuset (KI SÖS), Karolinska Institutet, Stockholm, Sweden
| | - M Dahlberg
- Department of Surgery, Södersjukhuset, Stockholm, Sweden
| | - G Heinius
- Department of Clinical Science and Education Södersjukhuset (KI SÖS), Karolinska Institutet, Stockholm, Sweden.,Department of Surgery, Södersjukhuset, Stockholm, Sweden
| | - J Nordberg
- Bilddiagnostiskt Centrum (BDC), Södersjukhuset, Stockholm, Sweden
| | - J Gustafsson
- Bilddiagnostiskt Centrum (BDC), Södersjukhuset, Stockholm, Sweden
| | - C Nordenvall
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.,Center for Digestive Disease, Division of Coloproctology, Karolinska University Hospital, Stockholm, Sweden
| | - G Sandblom
- Department of Clinical Science and Education Södersjukhuset (KI SÖS), Karolinska Institutet, Stockholm, Sweden.,Department of Surgery, Södersjukhuset, Stockholm, Sweden
| | - P Farahnak
- Department of Clinical Science and Education Södersjukhuset (KI SÖS), Karolinska Institutet, Stockholm, Sweden.,Department of Surgery, Södersjukhuset, Stockholm, Sweden
| | - Å H Everhov
- Department of Clinical Science and Education Södersjukhuset (KI SÖS), Karolinska Institutet, Stockholm, Sweden.,Department of Surgery, Södersjukhuset, Stockholm, Sweden.,Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
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Watanabe T, Miyata H, Konno H, Kawai K, Ishihara S, Sunami E, Hirahara N, Wakabayashi G, Gotoh M, Mori M. Prediction model for complications after low anterior resection based on data from 33,411 Japanese patients included in the National Clinical Database. Surgery 2017; 161:1597-1608. [PMID: 28153378 DOI: 10.1016/j.surg.2016.12.011] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2016] [Revised: 12/02/2016] [Accepted: 12/06/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND Low anterior resection is associated with a relatively high incidence of postoperative morbidities, including anastomotic leakage and other operative site infections, which sometimes result in postoperative mortality. Therefore, recognition of the incidence and risk factors of postoperative complications following low anterior resection is essential. METHODS Data from the National Clinical Database on patients who had undergone low anterior resection in 2011 and 2012 were retrospectively analyzed. Multiple logistic regression analyses were performed to generate predictive models of postoperative complications. Receiver-operator characteristic curves were generated, and the concordance index was used to assess the model's discriminatory ability. RESULTS The number of patients who had undergone low anterior resection was 33,411. Seven complications, namely, overall operative site infections except for leakage, anastomotic leakage, urinary tract infection, pneumonia, renal failure, systemic sepsis, and cardiac events, were selected to construct statistical risk models. The concordance indices for the first 2 complications, which were dependent on the operative procedure, were relatively low (0.593-0.625), and the other 5, unrelated to operative procedures, showed high concordance indices (0.643-0.799). CONCLUSION This study created the world's second risk calculator to predict the complications of low anterior resection as a model based on mass nationwide data. In particular, this model is the first to predict anastomotic leakage.
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Affiliation(s)
- Toshiaki Watanabe
- Japanese Society of Gastroenterological Surgery, Database Committee Working Group, Tokyo, Japan.
| | - Hiroaki Miyata
- Japanese Society of Gastroenterological Surgery, Database Committee Working Group, Tokyo, Japan; National Clinical Database, Tokyo, Japan
| | - Hiroyuki Konno
- Japanese Society of Gastroenterological Surgery, Database Committee Working Group, Tokyo, Japan
| | - Kazushige Kawai
- Japanese Society of Gastroenterological Surgery, Tokyo, Japan
| | | | - Eiji Sunami
- Japanese Society of Gastroenterological Surgery, Tokyo, Japan
| | | | - Go Wakabayashi
- Japanese Society of Gastroenterological Surgery, Tokyo, Japan
| | - Mitsukazu Gotoh
- Japanese Society of Gastroenterological Surgery, Tokyo, Japan
| | - Masaki Mori
- National Clinical Database, Tokyo, Japan; Japanese Society of Gastroenterological Surgery, Tokyo, Japan
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Kawada K, Sakai Y. Preoperative, intraoperative and postoperative risk factors for anastomotic leakage after laparoscopic low anterior resection with double stapling technique anastomosis. World J Gastroenterol 2016; 22:5718-5727. [PMID: 27433085 PMCID: PMC4932207 DOI: 10.3748/wjg.v22.i25.5718] [Citation(s) in RCA: 89] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Revised: 05/30/2016] [Accepted: 06/13/2016] [Indexed: 02/06/2023] Open
Abstract
Anastomotic leakage (AL) is one of the most devastating complications after rectal cancer surgery. The double stapling technique has greatly facilitated intestinal reconstruction especially for anastomosis after low anterior resection (LAR). Risk factor analyses for AL after open LAR have been widely reported. However, a few studies have analyzed the risk factors for AL after laparoscopic LAR. Laparoscopic rectal surgery provides an excellent operative field in a narrow pelvic space, and enables total mesorectal excision surgery and preservation of the autonomic nervous system with greater precision. However, rectal transection using a laparoscopic linear stapler is relatively difficult compared with open surgery because of the width and limited performance of the linear stapler. Moreover, laparoscopic LAR exhibits a different postoperative course compared with open LAR, which suggests that the risk factors for AL after laparoscopic LAR may also differ from those after open LAR. In this review, we will discuss the risk factors for AL after laparoscopic LAR.
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Risk Factors for Anastomotic Leak After Colon Resection for Cancer: Multivariate Analysis and Nomogram From a Multicentric, Prospective, National Study With 3193 Patients. Ann Surg 2015; 262:321-30. [PMID: 25361221 DOI: 10.1097/sla.0000000000000973] [Citation(s) in RCA: 249] [Impact Index Per Article: 24.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To determine pre-/intraoperative risk factors for anastomotic leak after colon resection for cancer and to create a practical instrument for predicting anastomotic leak risk. BACKGROUND Anastomotic leak is still the most dreaded complication in colorectal surgery. Many risk factors have been identified to date, but multicentric prospective studies on anastomotic leak after colon resection are lacking. METHODS Fifty-two hospitals participated in this prospective, observational study. Data of 3193 patients, operated for colon cancer with primary anastomosis without stoma, were included in a prospective online database (September 2011-September 2012). Forty-two pre-/intraoperative variables, related to patient, tumor, surgical procedure, and hospital, were analyzed as potential independent risk factors for anastomotic leak (60-day follow-up). A nomogram was created to easily predict the risk of anastomotic leak for a given patient. RESULTS The anastomotic leak rate was 8.7%, and widely varied between hospitals (variance of 0.24 on the logit scale). Anastomotic leak significantly increased mortality (15.2% vs 1.9% in patients without anastomotic leak, P < 0.0001) and length of hospitalization (median 23 vs 7 days in uncomplicated patients, P < 0.0001). In the multivariate analysis, the following variables were independent risk factors for anastomotic leak: obesity [P = 0.003, odds ratio (OR) = 2.7], preoperative serum total proteins (P = 0.03, OR = 0.7 per g/dL), male sex (P = 0.03, OR = 1.6), ongoing anticoagulant treatment (P = 0.05, OR = 1.8), intraoperative complication (P = 0.03, OR = 2.2), and number of hospital beds (P = 0.04, OR = 0.95 per 100 beds). CONCLUSIONS Anastomotic leak after colon resection for cancer is a frequent, relevant complication. Patients, surgical technique, and hospital are all important determining factors of anastomotic leak risk.
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McDermott FD, Heeney A, Kelly ME, Steele RJ, Carlson GL, Winter DC. Systematic review of preoperative, intraoperative and postoperative risk factors for colorectal anastomotic leaks. Br J Surg 2015; 102:462-79. [PMID: 25703524 DOI: 10.1002/bjs.9697] [Citation(s) in RCA: 580] [Impact Index Per Article: 58.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2014] [Revised: 09/09/2014] [Accepted: 10/08/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND Anastomotic leak (AL) represents a dreaded complication following colorectal surgery, with a prevalence of 1-19 per cent. There remains a lack of consensus regarding factors that may predispose to AL and the relative risks associated with them. The objective was to perform a systematic review of the literature, focusing on the role of preoperative, intraoperative and postoperative factors in the development of colorectal ALs. METHODS A systematic review was performed to identify adjustable and non-adjustable preoperative, intraoperative and postoperative factors in the pathogenesis of AL. Additionally, a severity grading system was proposed to guide treatment. RESULTS Of 1707 papers screened, 451 fulfilled the criteria for inclusion in the review. Significant preoperative risk factors were: male sex, American Society of Anesthesiologists fitness grade above II, renal disease, co-morbidity and history of radiotherapy. Tumour-related factors were: distal site, size larger than 3 cm, advanced stage, emergency surgery and metastatic disease. Adjustable risk factors were: smoking, obesity, poor nutrition, alcohol excess, immunosuppressants and bevacizumab. Intraoperative risk factors were: blood loss/transfusion and duration of surgery more than 4 h. Stomas lessen the consequences but not the prevalence of AL. In the postoperative period, CT is the most commonly used imaging tool, with or without rectal contrast, and a C-reactive protein level exceeding 150 mg/l on day 3-5 is the most sensitive biochemical marker. A five-level classification system for AL severity and appropriate management is presented. CONCLUSION Specific risk factors and their potential correction or indications for stoma were identified. An AL severity score is proposed to aid clinical decision-making.
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Affiliation(s)
- F D McDermott
- Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland
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Risk factor evaluation for postoperative complications in laparoscopic colorectal surgery by a classic severity grading system. Tumour Biol 2014; 35:8115-23. [PMID: 24840635 DOI: 10.1007/s13277-014-2016-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Accepted: 04/23/2014] [Indexed: 01/27/2023] Open
Abstract
Using the uniform complication grading system to evaluate postoperative complications after laparoscopic colorectal surgery is the purpose of the present study. Surgical complications were defined as grades I, II, III, IV, and V recommended by Dindo et al. Patients were categorized into three pairs: complication group (CG) and non-complication group (NCG), minor complication group (MiCG, grades I-II) and non-minor complication group (NMiCG), and major complication group (MaCG, grades III-V) and non-major complication group (NMaCG); of the 570 patients, 431 patients were discharged with no complications, and 174 complications occurred in 119 patients. The percent of grades I, II, III, IV, and V complications were 4.7, 20, 4.7, 0.7, and 0.4 %, respectively. Complications were significantly associated with male gender, larger tumor volume, and more estimated blood loss (EBL). The multivariate analysis revealed that male and EBL ≥150 ml were found to be independent predictors of postoperative complications. In subgroup analysis, patients with larger tumor volume were at significantly higher risk of postoperative major complications, and male gender and EBL ≥150 ml remained independent predictors of developing minor postoperative complications. Patients with postoperative complications would significantly experience longer hospital stay, later fluid intake, and delayed urinary catheter removal. Male, larger tumor volume, and more EBL were significant risk factors for laparoscopic colorectomy.
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Changes in Plasma Levels of Serotonin and 5-Hydroxyindoleacetic Acid and Population of Serotonin-Secreting Cells in Small and Large Intestine of Wistar Rats in Hypo- and Hyperandrogenemia. Bull Exp Biol Med 2013; 154:677-80. [DOI: 10.1007/s10517-013-2028-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Blood pressure and mesenteric vascular reactivity in spontaneously hypertensive rats 7 months after gonadectomy. J Cardiovasc Pharmacol 2011; 57:357-64. [PMID: 21383593 DOI: 10.1097/fjc.0b013e31820b7dc9] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE Sexual dimorphism in the degree of high blood pressure (BP) has been observed in both animal and human hypertension. However, the mechanisms are still poorly understood. We tested the hypothesis that long-term loss of sex steroids promotes changes in mesenteric vascular reactivity that impact the maintenance of hypertension in the spontaneously hypertensive rats (SHR). METHODS Male SHR were sham operated (M-SHAM) or castrated (M-CX), and female SHR were sham-operated (F-SHAM) or ovariectomized (F-OVX) at 3 weeks of age. Seven months later, BP was measured in anesthetized rats, and vascular responsiveness was evaluated in the isolated perfused mesentery. RESULTS Mean arterial BP (mm Hg) was significantly greater in M-SHAM (186 ± 6) compared with F-SHAM (159 ± 5). Gonadectomy reduced BP in male SHR (M-CX: 160 ± 4) but had no significant effect in female SHR (F-OVX: 153 ± 7). Norepinephrine-induced constriction was similar in all groups. Gonadectomy attenuated serotonin-induced vasoconstriction in the mesentery. Acetylcholine (ACh)- and isoproterenol (ISO)-induced vasodilation was greater in female than male SHR. Ovariectomy of female SHR blunted ACh and ISO dilatory responses. ISO dose-response curves were shifted to the left in castrated male SHR. CONCLUSIONS Gonadectomy exerts long-term effects on mesenteric vascular reactivity and hypertension in the SHR.
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Kennelly R, Conneely JB, Bouchier-Hayes DJ, Winter DC. Electrical field stimulation promotes anastomotic healing in poorly perfused rat colon. Int J Colorectal Dis 2011; 26:339-44. [PMID: 20809425 DOI: 10.1007/s00384-010-1053-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/18/2010] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Hypoperfusion of the bowel is a risk factor for anastomotic failure. Electrical field stimulation has been shown to improve repair in ischemic tissue, but its influence in hypoperfused colon has not been investigated. The hypothesis of this experimental animal study was that electrical field stimulation improves anastomotic healing in ischemic bowel. MATERIALS AND METHODS Thirty rats were divided evenly into three groups: control, ischemia/placebo, and ischemia/test group. Ischemia was induced by ligation of the arterial supply to the proximal colon. The watershed area was identified and transected. Field stimulation was achieved by application of negatively charged diethylaminoethyl Sephadex beads in methylcellulose gel to the colonic epithelium prior to anastomosis. The placebo group had methylcellulose gel only applied and control animals had anastomosis only. Anastomotic strength was measured using anastomotic bursting pressure and hydroxyproline content. Systemic effect was investigated via interleukin-6 and vascular endothelial growth factor assay. RESULTS The ischemia/electrical field stimulation (EFS) group had significantly increased bursting pressure and hydroxyproline content in comparison with the placebo group (P < 0.001). Serum cytokine levels were unaffected. CONCLUSION Negatively charged EFS improves anastomotic healing in hypoperfused colon without induction of systemic cytokines and has potential as a local treatment in high-risk bowel anastomosis.
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Affiliation(s)
- Rory Kennelly
- Institute for Clinical Outcomes, Research and Education, St Vincent's University Hospital, Dublin 00004, Ireland.
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Ba ZF, Chaudry IH. Role of estrogen receptor subtypes in estrogen-induced organ-specific vasorelaxation after trauma-hemorrhage. Am J Physiol Heart Circ Physiol 2008; 295:H2061-7. [PMID: 18805896 DOI: 10.1152/ajpheart.00707.2008] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Although endothelin-1 (ET-1)-induced organ hypoperfusion after trauma-hemorrhage is improved by estrogen administration, it remains unclear whether estrogen receptor (ER) subtypes play any role in the attenuation of ET-1-induced vasoconstriction in any specific organ bed. To investigate this, isolated perfusion experiments in the heart, liver, small intestine, kidney, and lung were carried out in sham, at the time of maximum bleedout (MBO; i.e., 5-cm midline incision, with removal of 60% of circulating blood volume over 45 min to maintain a mean blood pressure of 40 mmHg), and 2 h after trauma-hemorrhage and resuscitation (T-H/R). Organ-specific ET-1-induced vasoconstriction was evaluated, and the effects of 17beta-estradiol (E2) and ER-specific agonists propylpyrazole triol (PPT; ERalpha agonist) and diarylpropionitrile (DPN; ERbeta agonist) were determined. ET-1 induced the greatest vasoconstriction in sham animals, with the strongest response in the kidneys, followed by the small intestine and liver. ET-1-induced responses were weakest in the heart and lungs. ET-1-induced vasoconstriction was evident at the time of MBO but was significantly decreased at 2 h after T-H/R. ERbeta plays an important role in cardiac performance, as evidenced by improved heart performance (+dP/dt) in the presence of DPN. DPN also induced a greater effect than PPT in the reduction of ET-1-induced vasoconstriction in the kidneys and lungs. In contrast, PPT attenuated ET-1-induced vasoconstriction in the liver, whereas both DPN and PPT were equally effective in the small intestine. The increased +dP/dt values induced by E2, DPN, or PPT were evident at the time of MBO but were significantly decreased at 2 h after T-H/R. These data indicate that the effects of ET-1 on vasoconstriction and the role of ER subtypes in estrogen-induced vasorelaxation are organ specific and temporally specific after trauma-hemorrhage.
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Affiliation(s)
- Zheng F Ba
- Center for Surgical Research, University of Alabama, 1670 Univ. Blvd., G094 Volker Hall, Birmingham, AL 35294-0019, USA
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Deitch EA, Feketeova E, Lu Q, Zaets S, Berezina TL, Machiedo GW, Hauser CJ, Livingston DH, Xu DZ. RESISTANCE OF THE FEMALE, AS OPPOSED TO THE MALE, INTESTINE TO I/R-MEDIATED INJURY IS ASSOCIATED WITH INCREASED RESISTANCE TO GUT-INDUCED DISTANT ORGAN INJURY. Shock 2008; 29:78-83. [PMID: 17666951 DOI: 10.1097/shk.0b013e318063e98a] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
We tested the hypothesis that the female intestine is more resistant to gut I/R injury than the male intestine by comparing the effects of the isolated pure gut I/R superior mesenteric artery occlusion (SMAO) model on gut morphology and whether SMAO-induced distant organ injury (lung, bone marrow [BM], neutrophils, and red blood cells [RBCs]) would differ between male and proestrus female rats. At 6 or 24 h after SMAO or sham SMAO, gut injury, lung permeability, pulmonary neutrophil sequestration, RBC deformability, and BM RBC and white blood cell progenitor growth were measured, as was the ability of the plasma from these rats to activate naive rat neutrophils. At both 6 and 24 h after SMAO, the female rats had significantly less intestinal injury and reduced gut-induced lung injury, BM suppression, RBC dysfunction, and neutrophil activation than male rats subjected to SMAO. These results indicate that the resistance of proestrus female rats to gut injury and gut-induced distant organ injury is greater than that observed in male rats.
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Affiliation(s)
- Edwin A Deitch
- Department of Surgery, New Jersey Medical School, UMDNJ, Newark, NJ 07103, USA.
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El-Assal ON, Radulescu A, Besner GE. Heparin-binding EGF-like growth factor preserves mesenteric microcirculatory blood flow and protects against intestinal injury in rats subjected to hemorrhagic shock and resuscitation. Surgery 2007; 142:234-42. [PMID: 17689691 DOI: 10.1016/j.surg.2007.04.003] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2007] [Revised: 04/04/2007] [Accepted: 04/06/2007] [Indexed: 10/23/2022]
Abstract
BACKGROUND The gut is highly susceptible to injury after hemorrhagic shock and resuscitation (HS/R) because of progressive mesenteric hypoperfusion. The aim of the current study was to evaluate the effect of heparin-binding EGF-like growth factor (HB-EGF) on mesenteric microcirculatory blood flow and intestinal injury in rats subjected to HS/R. METHODS HS/R was induced in adult rats, with some rats receiving HB-EGF (600 mug/kg) IV at the onset of resuscitation (HS/R+HB-EGF) and others receiving vehicle only (HS/R). FITC-dextran was administered intra-arterially to evaluate mesenteric microcirculation, and intestinal damage and restitution were evaluated histologically. Data were expressed as mean +/- SE, with P < .05 considered statistically significant. RESULTS Microcirculatory blood flow was significantly reduced 1 hour after HS/R. HS/R+HB-EGF rats had significantly increased microcirculatory flow compared with HS/R rats at 1 hour (4.5 +/- 0.43 vs 2.64 +/- 0.46, P < .05) and 3 hours (8.04 +/- 1.58 vs 2.89 +/- 0.63, P < .05) after HS/R. HS/R+HB-EGF rats had significantly less intestinal damage compared with HS/R rats 3 hours after resuscitation (2.04 +/- 0.5 vs 3.08 +/- 0.5, P < .05), along with significantly fewer incompetent (nonresurfaced, nonhealed) villi, which is indicative of improved restitution. CONCLUSIONS HB-EGF significantly improved postresuscitation microcirculatory blood flow in rats subjected to HS/R, associated with significantly decreased intestinal damage and increased restitution. These results suggest that HB-EGF may be a useful therapeutic agent that improves intestinal blood flow in patients with intestinal injury secondary to hemorrhagic shock.
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Affiliation(s)
- Osama N El-Assal
- Department of Pediatric Surgery, Children's Hospital, Columbus, Ohio, USA
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Baccari MC, Nistri S, Vannucchi MG, Calamai F, Bani D. Reversal by relaxin of altered ileal spontaneous contractions in dystrophic (mdx) mice through a nitric oxide-mediated mechanism. Am J Physiol Regul Integr Comp Physiol 2007; 293:R662-8. [PMID: 17522128 DOI: 10.1152/ajpregu.00214.2007] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Altered nitric oxide (NO) production/release is involved in gastrointestinal motor disorders occurring in dystrophic (mdx) mice. Since the hormone relaxin (RLX) can upregulate NO biosynthesis, its effects on spontaneous motility and NO synthase (NOS) expression in the ileum of dystrophic (mdx) mice were investigated. Mechanical responses of ileal preparations were recorded in vitro via force-displacement transducers. Evaluation of the expression of NOS isoforms was performed by immunohistochemistry and Western blot. Normal and mdx mice were distributed into three groups: untreated, RLX pretreated, and vehicle pretreated. Ileal preparations from the untreated animals showed spontaneous muscular contractions whose amplitude was significantly higher in mdx than in normal mice. Addition of RLX, alone or together with l-arginine, to the bath medium depressed the amplitude of the contractions in the mdx mice, thus reestablishing a motility pattern typical of the normal mice. The NOS inhibitor N(G)-nitro-L-arginine (L-NNA) or the guanylate cyclase inhibitor ODQ reversed the effects of RLX. In RLX-pretreated mdx mice, the amplitude of spontaneous motility was reduced, thus resembling that of the normal mice, and NOS II expression in the muscle coat was increased in respect to the vehicle-pretreated mdx animals. These results indicate that RLX can reverse the altered ileal motility of mdx mice to a normal pattern, likely by upregulating NOS II expression and NO biosynthesis in the ileal smooth muscle.
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Affiliation(s)
- M C Baccari
- Department of Physiological Sciences, University of Florence, V.le G.B. Morgagni 63, I-50134, Florence, Italy.
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Júnior UL, Cordellini S. Differential vascular adaptive response to stress exposure in male and female rats: role of gonadal hormones and endothelial cells. Stress 2007; 10:27-36. [PMID: 17454964 DOI: 10.1080/10253890601135426] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
UNLABELLED Although there are reports concerning a vascular adaptive response to stress in males, this is not yet defined in females. The aim of this study was to delineate functional gender differences in the rat vascular adaptive response to stress and to determine the ability of sex hormones to modulate the stress-induced vascular adaptive response. Responses to noradrenaline were evaluated in aortas, with and without endothelium, from intact, gonadectomized and gonadectomized-hormone-replaced males and females submitted or not to stress (2-h immobilization). Reactivity of the aorta of stressed and non-stressed intact males and females (n = 6-14 per group) was also examined in the presence of L-NAME or indomethacin. Stress decreased and gonadectomy increased maximal responses to noradrenaline in aortas with intact endothelium from both genders. Stress also reduced noradrenaline potency in males. In females, but not males, stress decreased the gonadectomy-induced noradrenaline hyper-reactivity to near that of intact non-stressed rats. Hormone replacement restored the gonadectomy-induced impaired vascular adaptive response to stress. L-NAME, but not indomethacin, abolished the stress-induced decrease in aorta reactivity of males and females. None of the procedures altered reactivity of aortas denuded of endothelium. CONCLUSION Stress-induced vascular adaptive responses show gender differences. The magnitude of the adaptive response is dependent on testicular hormones and involves endothelial nitric oxide-system hyperactivity.
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Affiliation(s)
- Ubirajara Lanza Júnior
- Department of Pharmacology, Institute of Biosciences, University Estadual Paulista, 18618-000, Rubião Júnior s/n, Botucatu, São Paulo. Brasil
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Yoon SJ, Kim JS, Min BS, Kim NK, Baik SH, Lee KY, Sohn SK, Cho JH. Risk Factors for Anastomotic Leakage after a Low Anterior Resection for Rectal Cancer. JOURNAL OF THE KOREAN SOCIETY OF COLOPROCTOLOGY 2007. [DOI: 10.3393/jksc.2007.23.5.365] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Affiliation(s)
- Seok-jun Yoon
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jin-soo Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Byung-so Min
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Nam-Kyu Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Seung-Hyuk Baik
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Kang-Young Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Seung-Kook Sohn
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jang-Hwan Cho
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
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Lipska MA, Bissett IP, Parry BR, Merrie AEH. Anastomotic leakage after lower gastrointestinal anastomosis: men are at a higher risk. ANZ J Surg 2006; 76:579-85. [PMID: 16813622 DOI: 10.1111/j.1445-2197.2006.03780.x] [Citation(s) in RCA: 199] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Anastomotic leakage is the most important complication specific to intestinal surgery. The aim of this study was to review the anastomotic leakage rates in a single Colorectal Unit and to evaluate the risk factors for anastomotic leakage after lower gastrointestinal anastomosis. METHODS A total of 541 consecutive operations involving anastomoses of the colon and rectum that were carried out between 1999 and 2004 at a single colorectal unit were reviewed. Data concerning 35 variables, relating to patient, tumour and surgical factors, were recorded. Outcomes with respect to anastomotic leakage and mortality were recorded. Data were analysed using univariate and multivariate analyses and odds ratios (OR) calculated. RESULTS The overall rate of anastomotic leakage was 6.5% (35 of 541). The most frequently carried out operations were right hemicolectomy and anterior resection of the rectum, with leak rates of 2.2 and 7.4%, respectively. Univariate analysis showed that male gender (OR = 3.5), previous abdominal surgery (OR = 2.4), Crohn's disease (OR = 3.3), rectal cancer < or =12 cm from the anal verge (OR = 5.4) and prolonged operating time (OR = 2.8) were factors significantly associated with anastomotic leakage. Male gender, a history of previous abdominal surgery and the presence of a low cancer remained significant after multivariate analysis. The risk of anastomotic leakage increased when two or more risk factors were present (P < 0.01). The overall mortality was 3.7% and was higher in patients with anastomotic leakage (14.3%; P = 0.01). CONCLUSIONS Male gender, previous abdominal surgery and low rectal cancer are associated with increased anastomotic leakage rates. These have important implications during preoperative patient counselling and decision-making regarding defunctioning stoma formation.
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Abstract
Gonadal steroids are metabolized in target cells and then interact with specific receptors to exert genomic and nongenomic effects. Complex feedback loops that involve the immune-neuroendocrine axis, limbic system, and gonadal steroids play a vital role in the adaptation to critical illness. Preclinical studies demonstrate adverse physiological effects of androgens on the cardiovascular and immune systems despite its purported anabolic effects. Similar models also demonstrate salutary effects of estrogens on these systems. Thus, during the catabolic phases of acute and chronic critical illness, estrogen, and not androgen, therapy may prove to be a valuable intervention. However, during the post-critical illness recovery phase, when anabolism is critical, androgen therapy may still be useful and safe.
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Affiliation(s)
- Jeffrey I Mechanick
- Division of Endocrinology, Diabetes and Bone Disease, Mount Sinai School of Medicine, 1192 Park Avenue, New York, NY 10128, USA.
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Szabó A, Vollmar B, Boros M, Menger MD. Gender differences in ischemia-reperfusion-induced microcirculatory and epithelial dysfunctions in the small intestine. Life Sci 2006; 78:3058-65. [PMID: 16413039 DOI: 10.1016/j.lfs.2005.12.012] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2005] [Accepted: 12/05/2005] [Indexed: 11/27/2022]
Abstract
Female sex hormones have been reported to preserve endothelial integrity and to reduce inflammation. However, gender-related differences in the intestinal mucosal barrier function during compromised perfusion after ischemia and transplantation have not been defined. Herein, we applied intravital microscopy to determine the mucosal epithelial and intestinal microcirculatory responses in ileal villus and longitudinal muscle layers in a murine model of 30-min intestinal ischemia and 90-min reperfusion. In male animals, the entire reperfusion period was characterized by a significantly increased epithelial permeability. This was associated with an early leukocytic inflammatory response and late alterations in functional capillary density, capillary red blood cell velocity and mitochondrial redox state. In contrast, the female intestine exhibited a delayed increase in epithelial permeability during postischemic reperfusion. This was associated with a late leukocytic inflammatory response which did not affect the microcirculatory function. Nonetheless, at the end of the 90-min reperfusion period, the neutrophilic infiltration and structural mucosal disintegration in the female intestine were found to be pronounced to a similar extent as in the male intestine. These results suggest that in small intestinal ischemia-reperfusion the leukocytic inflammatory response and microcirculatory dysfunction develop more rapidly and are initially more pronounced in males, but the hormonal status in females is not capable of preventing the final manifestations of reperfusion injury.
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Affiliation(s)
- Andrea Szabó
- Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, D-66421 Germany
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Yokoyama Y, Nimura Y, Nagino M, Bland KI, Chaudry IH. Current Understanding of Gender Dimorphism in Hepatic Pathophysiology1. J Surg Res 2005; 128:147-56. [PMID: 15939435 DOI: 10.1016/j.jss.2005.04.017] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2005] [Revised: 01/15/2005] [Accepted: 04/08/2005] [Indexed: 10/25/2022]
Abstract
Studies have shown gender dimorphic response of the liver for various hepatic stresses including ischemia/reperfusion, hemorrhagic shock-resuscitation, hepatectomy, liver cirrhosis, endotoxemia, and chronic alcoholic consumption. The mechanisms responsible for the gender dimorphic response include differences in pro-inflammatory cytokine release, production of reactive oxygen species, and alteration in hepatic vasoregulatory action. These effects were shown to be modulated by circulating sex steroid levels. In this regard, modulation of sex steroid levels by agents/drugs has been proposed as a therapeutic option for preventing hepatic damage in various hepatic stress models. Further elucidation of precise mechanisms responsible for the gender-related differences in the hepatic pathophysiology is essential for the potential clinical application of sex hormone modulation therapy. In this article, current progress in our understanding the gender difference in the hepatic pathophysiology under the condition of hepatic stress is reviewed and discussed.
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Affiliation(s)
- Yukihiro Yokoyama
- Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294-0019, USA
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Ba ZF, Shimizu T, Szalay L, Bland KI, Chaudry IH. Gender differences in small intestinal perfusion following trauma hemorrhage: the role of endothelin-1. Am J Physiol Gastrointest Liver Physiol 2005; 288:G860-5. [PMID: 15550555 DOI: 10.1152/ajpgi.00437.2004] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Although gender differences in intestinal perfusion exist following trauma-hemorrhage (T-H), it remains unknown whether endothelin-1 (ET-1) plays any role in these dimorphic responses. To study this, male, proestrus female (female), and 17 beta-estradiol (E2)-treated male rats underwent midline laparotomy, hemorrhagic shock (blood pressure 40 mmHg, 90 min), and resuscitation (Ringer lactate, 4X shed blood volume, 1 h). Two hours thereafter, intestinal perfusion flow (IPF) was measured using isolated intestinal perfusion. The IPF in sham-operated males was significantly lower than those in other groups and decreased markedly following T-H. In contrast, no significant decrease in IPF was observed in females and E2 males following T-H. The lower IPF in sham-operated males was significantly elevated by ET(A) receptor antagonist (BQ-123) administration and was similar to that seen in sham-operated females. The decreased IPF in males after T-H was also attenuated by BQ-123 administration. The intestinal ET-1 levels in sham-operated males were significantly higher than in other groups. Although plasma and intestinal ET-1 levels increased significantly after T-H in all groups, they were highest in males. Plasma E2 levels in females and E2 males were significantly higher than in males; however, they were not affected by T-H. There was a negative correlation between plasma ET-1 and E2 following T-H. Thus ET-1 appears to play an important role in intestinal perfusion failure following T-H in males. Because E2 can modulate this vasoconstrictor effect of ET-1, these findings may partially explain the previously observed salutary effect of estrogen in improving intestinal perfusion following T-H in males.
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Affiliation(s)
- Zheng F Ba
- Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, 1670 Univ. Boulevard, Volker Hall, Rm. G094, Birmingham, Alabama 35294-0019, USA
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